Trichostatin C attenuates TNFα-induced inflammation in endothelial cells by up-regulating Krüppel-like factor 2 / 药学学报

Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.

Exploration on the training model of applied undergraduate pharmacy talents under the perspective of industry education integration / 中华医学教育探索杂志

This research analyzes and explores the elements of the industry education integration in the process of pharmacy talent training from two aspects: collaborative education (professional construction, curriculum co-construction, skill deepening and talent transfer) and collaborative innovation (base expansion, technological research and completion innovation). Besides, this research also explores the outstanding performance of School of Pharmacy of Xiamen Medical College in talent training of the industry education integration. The results show that through the construction of collaborative education and collaborative innovation, the elements of the industry education integration in the cultivation of pharmacy talents in the school have become increasingly prominent, and the forms have been gradually diversified, which have promotion and guiding significance for other majors in our school to develop the industry education integration.

Study on the susceptibility genes that mediate the resistance of Helicobacter pylori to clarithromycin and levofloxacin based on comprehensive antibiotic research database comparison / 中华消化杂志

Objective:Taking clinical strains of Helicobacter pylori ( H. pylori) with different antimicrobial resistance as the research object, to explore the new genes related to the resistance of H. pylori to clarithromycin (CLA) and levofloxacin (LVX) based on whole-genome sequencing. Methods:From September 1st, 2016 to August 31st, 2019, 1 749 patients with upper gastrointestinal symptoms and positive 13C urea breath test who visited the Department of Gastroenterology and Hepatology, the University of Hong Kong-Shenzhen Hospital were enrolled. After gastric mucosal biopsy, H. pylori was isolated and cultured from gastric mucosa. Ninety H. pylori strains were successfully preserved. According to the results of in vitro drug sensitivity test, a total of 40 strains including 10 strains with single-drug resistance to CLA (CLA group), 10 strains with single-drug resistance to LVX (LVX group), 10 strains with dual-resistance to CLA and LVX (dual resistance group) and 10 strains sensitive to CLA, LVX, amoxicillin, furazolidone, tetracycline and metronidazole (all sensitive group) were screened out. By whole-genome sequencing and comparison to the comprehensive antibiotic research database (CARD), single nucleotide variations (SNV) and indels were analyzed, genes related to H. pylori resistance to CLA and LVX were screened out and the differences of new genes among 4 groups were analyzed. Independent sample t test, one-way analysis of variance, least significant difference method and chi-square test were used for statistical analysis. Results:Among the 4 groups there were no statistically significant differences in the number of SNV (74 952.00±8 755.21, 77 128.10±3 191.35, 78 639.90±601.23 and 77 474.60±2 421.05) and Indels (2 582.20±265.45, 2 653.60±108.37, 2 667.10±43.82 and 2 641.10±80.25) (all P>0.05). Compared to CARD, a total of 223 drug resistance-related genes were detected, of which 19 genes related to CLA mono-resistance in CLA group, 24 genes related to LVX mono-resistance in LVX group, 16 genes related to CLA mono-resistance, 14 genes related to LVX mono-resistance, and 12 dual resistance-related genes in dual resistance group, and 11 genes related to CLA mono-resistance, 17 genes related to LVX mono-resistance, and 13 dual resistance-related genes in all sensitive group. Among the genes related to CLA mono-resistance, the detection rates of erythromycin esterase gene ( ere)B in CLA group, LVX group, dual resistance group and all sensitive group were 0/10, 0/10, 3/10, 0/10, respectively, and the difference was statistically significant( χ2=5.79, P=0.049). The detection rate of erythromycin ribosomal methylase gene ( erm) family in CLA group and dual resistance group was higher than that in LVX group and all sensitive group (45.0%, 9/20 vs. 10.0%, 2/20), and the difference was statistically significant ( χ2=6.14, P=0.013). The detection rates of free methionine-(R)-sulfoxide reductase gene ( msrC) in CLA group, LVX group, dual resistance group and all sensitive group were 10/10, 7/10, 6/10, 4/10, respectively, and the difference was statistically significant ( χ2=8.97, P=0.030). Among the genes related to LVX mono-resistance, the detection rate of quinolone resistance pentapeptide repeat protein gene ( qnr) family in LVX group and dual resistance group was higher than that in CLA group and all sensitive group (60.0%, 12/20 vs. 25.0%, 5/20), and the difference was statistically significant ( χ2=5.01, P=0.025). The detection rates of qnrB4 in CLA group, LVX group, dual resistance group and all sensitive group were 1/10, 3/10, 7/10, 1/10, respectively, and the difference was statistically significant ( χ2=10.17, P=0.010). The number of efflux transporter genes related to CLA mono-resistance in 4 groups were less than those of LVX mono-resistance and dual drug resistance (11 vs. 29 and 11 vs. 23), and the differences were statistically significant ( χ2=11.87, 5.80; P=0.001, 0.016). The detected numbers of LVX resistance-related efflux transport genes in CLA group, LVX group, dual resistance group and all sensitive group were 28, 40, 24 and 27, respectively, and the difference was statistically significant ( χ2=10.26, P=0.016). Conclusions:Erm family and msrC may be important genes that mediate the resistance of H. pylori to CLA, and qnr family is related to mediating the resistance of H. pylori to LVX. Efflux transport genes may play a synergistic role in the process of drug efflux, and are more likely to mediate H. pylori resistance to LVX.

Manual therapy combined with posterior percutaneous endoscopic cervical decompression for the treatment of cervical spondylotic radiculopathy / 中国骨伤

OBJECTIVE@#To explore the clinical efficacy and safety of manual therapy combined with posterior percutaneous endoscopic cervical decompression(PECD) in the treatment of intractable cervical spondylotic radiculopathy.@*METHODS@#From May 2016 to May 2018, 23 CSR patients who responded poorly to conservative treatment for at least 6 weeks underwent the combination management. Firstly, the patients received the posterior percutaneous endoscopic cervical decompression routine care for the following 4 weeks and manual therapy for another 4 weeks. A total of 23 patients were followed up, including 14 males and 9 females, the age ranged from 29 to 78 years old with an average of (50.30±12.28) years, the course of disease was 3 to 24 months with an average of (9.74±5.76) months. The lesion segment involved C4,5 in 4 cases, C5,6 in 13 cases, C6,7 in 6 cases. The visual analogue scale (VAS), neck disability index (NDI), changes of cervical physiological curvature and interbody stability, adverse events were observed before and after operation. The follow-up time points were before operation, 1 day after operation and 1, 3 and 6 months after operation.@*RESULTS@#All patients successfully completed the operation and manual treatment for 4 to 8 times. Among the 29 cases, 23 patients were followed up for more than 6 months. There was no spinal cord and nerve root injury during the treatment and follow-up. Operation time was from 80 to 120 min with a median of 90 min;intraoperative blood loss was from 35 to 80 ml with a median of 50 ml. NDI, VAS of neck, shoulder and arm each period after operation were significantly lower than those before PECD(P<0.05), while there were no significant improvement in cervical physiological curvature and target segment intervertebral space height(P>0.05);there was no significant change in interbody stability (P>0.05). After received the manual therapy, NDI significantly decreased (P<0.05), however, there was no significant difference in VAS of neck, shoulder and arm, physiological curvature of cervical spine and intervertebral space height of target segment compared with that before manual treatment (P>0.05);there was no significant change in interbody stability (P>0.05).@*CONCLUSION@#Manual therapy combined with PECD in the treatment of intractable cervical spondylotic radiculopathy can not only quickly improve the symptoms, but also alleviate the residual symptoms after PECD safely and effectively, and can not cause obvious signs of accelerated instability of cervical adjacent segments in the short term.

Reconstruction of degree V defect of thumb: A case report / 中华显微外科杂志

In March 2014, a degree V defect of right thumb was reconstructed with a free right hallux nail flap combined with bone and tendon composite tissue of the 2nd toe in the Department of Hand Surgery, Ningbo No. 6 Hospital. A freed right superficial iliac circumflex artery perforator flap (SCIPF) and autologous iliac bone were used to repair the donor site of foot. The hand function was evaluated according to the upper limb function scoring system. Seven years after operation, the function of the right hand was significantly improved and the function of right foot was not significantly affected. According to the Michigan Hand Function Score, the result was 80 point. Functional recovery evaluated according to the Evaluation Standard of Reconstructed Thumb and Finger Functional of Hand Surgery of Chinese Medical Association, the result was excellent (14 point).

Reconstruction of 4 digits with defect of 10 digits: A case report / 中华显微外科杂志

A patient recovered partial hand functions by 4 reconstructed digits based on a pair of complete defect hands that lost all of 10 digits on March, 2014. The thumbs were reconstructed with bipedal nail flaps combined with iliac bone, the right index finger and left middle finger were reconstructed with the 2nd toes of feet. Bilateral superficial circumflex iliac artery rerforator flaps (SCIPF) were taken to repair the donor areas of feet. According to the DASH-Chinese upper limb function score system, the function of both hands was obviously improved in six and a half years after surgery. The function of both feet was not significantly affected.

Efficacy and safety of ticagrelor versus clopidogrel in Chinese patients with acute coronary syndrome treated with glycoprotein Ⅱb/Ⅲa receptor antagonist / 中华内科杂志

Objective:To explore the efficacy and safety of ticagrelor versus clopidogrel in acute coronary syndrome (ACS) Chinese patients using glycoprotein Ⅱb/Ⅲa inhibitor (GPI).Methods:The data from CCC-ACS (Improving Care for Cardiovascular Disease in China-ACS) project were systematically reviewed in ACS patients with GPI. The patients were divided into ticagrelor and clopidogrel groups. A logistic analysis and propensity score matching (PSM) were performed to compare occurrences of major cardiovascular events (MACE) and bleeding events between the two groups during hospitalization.Results:A total of 63 641 ACS patients were collected from 150 hospitals. Logistic regression analyses showed that there was no statistically significant difference in the reduction of MACE between ticagrelor and clopidogrel when using GPI ( OR=0.881, 95% CI 0.599-1.296; P=0.521). However, major bleeding rate was higher in the ticagrelor group than that in the clopidogrel group ( OR=1.401, 95% CI 1.075-1.852; P=0.013). Similar results were observed after PSM. No statistic difference in MACE between the ticagrelor and clopidogrel group ( OR=0.919, 95% CI 0.613-1.376; P=0.681). Major bleeding rate was higher in the ticagrelor group ( OR=1.559, 95% CI 1.130-2.150; P=0.007). Conclusion:In ACS patients with GPI, ticagrelor did not reduce MACE, but increased the major bleeding risk compared with clopidogrel.

Application of end-to-side anastomosis in personalised free ilioinguinal flap transfer / 中华显微外科杂志

Objective:To investigate the clinical application and effect of end-to-side anastomosis in personalised free ilioinguinal flap transfer.Methods:From March, 2015 to July, 2020, 88 patients with soft tissue (bone) defect of limbs were treated. Different ilioinguinal flaps were designed according to the wound condition of patients, which were 48 cases of free superficial circumflex iliacartery perforator flap, 7 cases of free superficial epigastric artery perforator flap, 19 cases of composite tissue flap with iliac bone, 8 cases of combined flap of superficial circumflex iliac artery and superficial abdominal wall artery, and 6 cases of superficial circumflex iliac artery and superficial abdominal wall artery lobulated flap. The area of the flap was 4.0 cm×6.0 cm-10.0 cm×30.0 cm. The artery and recipient artery were anastomosed end-to-side: 36 cases to radial artery; 12 cases to ulnar artery; 18 cases to dorsalis pedis artery; 15 cases to anterior tibial artery; 7 cases to posterior tibial artery. Venous anastomosis of skin flap: 42 cases were anastomosed with 2 veins, which were superficial vein of the same name and accompanying vein; 46 cases were anastomosed with 1 superficial vein of the same name. The accompanying vein of the flap was anastomosed end-to-side with the accompanying vein of the main artery of the recipient area, and the superficial vein of the same name was anastomosed end-to-end with the accompanying vein or subcutaneous superficial vein of the recipient artery. Follow-up includes flap blood supply, blood supply to the distal limbs, appearance of both the donor site and the recipient area, and patient satisfaction.Results:There were 83 cases of flaps survived successfully, and 5 cases of crisis. Among them, 2 cases had artery crisis at 48 h after surgery. After exploration, it was found that 1 case caused by arterial thrombosis, and 1 case compressed by the stapler that anastomoses the vein. The other 3 cases had venous crisis at 72 h after surgery: after exploration, it was found that caused by thrombosis at the venous anastomotic site. The average follow-up period was 10 (range, 3-24) months. All flaps survived after re anastomosis or vascular transposition. The donor site and recipient site of the flap healed well. The blood supply of the flap was good and the texture was soft. There was no blood supply disorder in the distal limb.Conclusion:The end-to-side anastomosis technique is suitable for all kinds of free flap transplantation in ilioinguinal region, with high vascular patency rate. It can not only solve the problem of thin vascular pedicle of donor site flap, but also retain the main artery of recipient limb without affecting the distal blood supply.

Efficacy of Different Doses of Daunorubicin Induced Chemotherapy in Patients with Newly Diagnosed Primary Acute Myeloid Leukemia Under 65 Years Old / 中国实验血液学杂志

OBJECTIVE@#To compare the efficacy and safety of different doses of daunorubicin combined with a standard dose of cytarabine as induction chemotherapy in newly diagnosed primary acute myeloid leukemia (AML) patients.@*METHODS@#The clinical data and outcome were retrospectively analyzed in 86 newly diagnosed primary AML patients who were under 65 years old and treated with daunorubicin combined with cytarabine (DA regimen) at West China Hospital of Sichuan University from January 2017 to June 2019. Patients were divided into 2 groups based on the dose of daunorubicin they received, 35 cases in the escalated-dose group ［75 mg/(m@*RESULTS@#Median follow-up time of all the patients was 15 months. The CR rate and MRD@*CONCLUSION@#The escalated dose of daunorubicin can induce higher complete remission rate, deeper remission and longer duration of remission without increasing adverse events in newly diagnosed primary AML patients.

The therapeutic dilemma of idiopathic granulomatous mastitis

INTRODUCTION@#Idiopathic granulomatous mastitis (IGM) is a rare, benign, chronic breast condition that can cause repeated abscesses or mass formation in bilateral breasts. The condition can severely impact the quality of life of affected women. This study aims to evaluate effective treatment modalities, as well as understand the demographics and clinical presentation of patients with IGM.@*METHODS@#An 11-year retrospective review was performed of patients diagnosed with IGM from 1 January 2008 to 31 December 2018 at a tertiary breast unit.@*RESULTS@#A total of 77 patients were included in the study. The median age at presentation was 36 years old. IGM presented most commonly as a breast lump (98.1%). The median number of flares was 2 (1-12). Of the 77 patients, 68.8% (53) were treated with antibiotics, 50.6% (39) with steroids, and 44.2% (34) underwent surgery, in the course of their IGM treatment. Forty-five (59.2%) of the 76 patients with IGM required a multimodal treatment approach to achieve remission. There was no significant difference in the number of flares no matter the initial treatment (@*CONCLUSION@#IGM is a clinical diagnosis. It is a rare, relapsing breast inflammatory condition that affects young females with no superior treatment modality. Smoking is associated with higher number of flares of IGM and should be discouraged in IGM patients.

Predictive value of tumor regression rate after induction chemotherapy for survival of patients with locally advanced nasopharyngeal carcinoma / 国际肿瘤学杂志

Objective:To investigate the predictive value of tumor regression rate after induction chemotherapy for survival of patients with locally advanced nasopharyngeal carcinoma.Methods:A total of 161 patients with stage Ⅲ-ⅣA nasopharyngeal carcinoma newly diagnosed at the Daping Hospital of Army Medical University from January 2009 to December 2012 were selected as the research subjects. The relationships between tumor size changes before and after induction chemotherapy and survival time were analyzed. Kaplan-Meier method was used to draw the survival curve accompanied with log-rank test. Cox regression analysis was used to analyze the risk factors affecting the prognosis of patients with nasopharyngeal carcinoma.Results:There were statistically significant differences in the tumor regression rate of primary lesions between N 1and N 2-3( Z=2.177, P=0.029), T 1-2and T 3-4( Z=-4.501, P<0.001)patients after induction chemotherapy. In N 1stage patients, the 5-year overall survival (OS) rates of patients with primary lesions achieving objective response ( n=18) and those without objective response ( n=19) after induction chemotherapy were 88.89% and 57.45%, and patients with cervical lymph node metastatic lesions achieving objective response ( n=19) and those without objective response ( n=18) were 86.72% and 49.10% respectively, with statistically significant differences ( χ2=6.023, P=0.014; χ2=7.441, P=0.006). In N 2-3stage patients, the 5-year OS rates of patients with primary lesions achieving objective response ( n=81) and those without objective response ( n=43) after induction chemotherapy were 77.56% and 50.70%, and patients with cervical lymph node metastatic lesions achieving objective response ( n=85) and those without objective response ( n=39) were 75.11% and 52.04% respectively, with significant differences ( χ2=8.037, P=0.005; χ2=7.268, P=0.007). Univariate Cox regression analysis showed that in patients with stage N 1, the tumor regression rate of primary lesions ( HR=0.048, 95% CI: 0.004-0.644, P=0.022), the efficacy of primary lesions ( HR=0.174, 95% CI: 0.037-0.830, P=0.028), the efficacy of cervical lymph node metastatic lesions ( HR=0.154, 95% CI: 0.033-0.725, P=0.017) after induction chemotherapy were significantly associated with OS; in N 2-3stage patients, the tumor regression rate of primary lesions ( HR=0.178, 95% CI: 0.056-0.564, P=0.003), the tumor regression rate of cervical lymph node metastatic lesions ( HR=0.081, 95% CI: 0.020-0.324, P<0.001), the efficacy of primary lesions ( HR=0.422, 95% CI: 0.228-0.781, P=0.006), the efficacy of cervical lymph node metastatic lesions ( HR=0.439, 95% CI: 0.238-0.813, P=0.009) after induction chemotherapy were significantly associated with OS. In multivariate Cox regression including N stage and tumor regression rate, N stage and efficacy, the interaction items were not statistically significant (all P>0.05). In T 1-2stage patients, the 5-year OS rates of patients with primary lesions achieving objective response ( n=45) and those without objective response ( n=13) after induction chemotherapy were 77.55% and 84.62%, and patients with cervical lymph node metastatic lesions achieving objective response ( n=43) and those without objective response ( n=15) were 78.89% and 80.00% respectively, with no significant differences ( χ2=0.239, P=0.625; χ2=0.005, P=0.943); in T 3-4stage patients, the 5-year OS rates of patients with primary lesions achieving objective response ( n=54) and those without objective response ( n=49) after induction chemotherapy were 78.90% and 45.00%, and patients with cervical lymph node metastatic lesions achieving objective response ( n=61) and those without objective response ( n=42) were 75.10% and 42.89% respectively, with significant differences ( χ2=13.615, P<0.001; χ2=12.752, P<0.001). Univariate Cox regression analysis showed that in patients with stage T 1-2, the tumor regression rate, the efficacy of primary lesions and cervical lymph node metastatic lesions after induction chemotherapy were not related to OS (all P>0.05); in T 3-4stage patients, the tumor regression rate of primary lesions ( HR=0.121, 95% CI: 0.033-0.444, P=0.001), the tumor regression rate of cervical lymph node metastatic lesions ( HR=0.126, 95% CI: 0.036-0.442, P=0.001), the efficacy of primary lesions ( HR=0.297, 95% CI: 0.150-0.588, P<0.001), the efficacy of cervical lymph node metastatic lesions ( HR=0.329, 95% CI: 0.173-0.625, P=0.001) after induction chemotherapy were significantly associated with OS. Multivariate Cox regression analysis showed that the interaction test of T stage and the efficacy of primary lesion trended to be statistically significant ( P=0.062). Conclusion:In patients with stage Ⅲ-ⅣA nasopharyngeal carcinoma, the responsiveness to induction chemotherapy in stage T 3-4patients has important value in predicting survival prognosis.

Anterior thalamic nuclei deep brain stimulation inhibits mossy fiber sprouting via 3',5'-cyclic adenosine monophosphate/protein kinase A signaling pathway in a chronic epileptic monkey model / 中华医学杂志(英文版)

BACKGROUND@#Anterior thalamic nuclei (ATN) deep brain stimulation (DBS) is an effective method of controlling epilepsy, especially temporal lobe epilepsy. Mossy fiber sprouting (MFS) plays an indispensable role in the pathogenesis and progression of epilepsy, but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown. This study aimed to investigate the effect of ATN-DBS on MFS, as well as potential signaling pathways by a kainic acid (KA)-induced epileptic model.@*METHODS@#Twenty-four rhesus monkeys were randomly assigned to control, epilepsy (EP), EP-sham-DBS, and EP-DBS groups. KA was injected to establish the chronic epileptic model. The left ATN was implanted with a DBS lead and stimulated for 8 weeks. Enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus. One-way analysis of variance, followed by the Tukey post hoc correction, was used to analyze the statistical significance of differences among multiple groups.@*RESULTS@#ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy. The number of ectopic granule cells was reduced in monkeys that received ATN stimulation (P < 0.0001). Levels of 3',5'-cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) in the hippocampus, together with Akt phosphorylation, were noticeably reduced in monkeys that received ATN stimulation (P = 0.0030 and P = 0.0001, respectively). ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions (all P < 0.0001).@*CONCLUSION@#ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells, which may be associated with the reduced MFS in chronic epilepsy. The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.

Safety and short-term efficacy of apatinib combined with oxaliplatin and S-1 in the conversion treatment for gastric cancer with peritoneal metastasis / 中华胃肠外科杂志

Objective: To investigate the safety and short-term efficacy of apatinib combined with oxaliplatin and S-1 in the conversion treatment for gastric cancer with different types of peritoneal metastasis. Methods: A prospective study "one arm exploratory clinical study of conversion therapy of apatinib with S-1 and oxaliplatin in the treatment of advanced gastric cancer" (clinical registration ChiCTR-ONC-17010430) from medical record database was retrospectively analyzed. Patients aged 18-70 years with gastric cancer peritoneal metastasis confirmed by histology and laparoscopic exploration, and had not receive radiotherapy, chemotherapy, targeted therapy or immunotherapy before were enrolled. Before operation, the patients received 6 cycles of S-1 (80-120 mg/d, d1-d14) and oxaliplatin (130 mg/m(2), d1), and 5 cycles of apatinib (500 mg/d, d1-d21) conversion regimen. Three weeks after chemotherapy, whether the operation was performed or not depending on re-evaluation and patient preference. The main outcome were adverse reactions, and the secondary outcome were objective remission rate (ORR), disease control rate (DCR), and overall survival (OS) rate. The follow-up period was up to May 2020. Results: A total of 27 patients with gastric cancer peritoneal metastasis were enrolled in this study. There were 13 males and 14 females, with a median age of 58 (30-68) years old. There were 9 cases of P1a, 5 cases of P1b, and 13 cases of P1c. There were 14 cases with 1-5 scores of PCI (peritoneal cancer index), and 13 cases with 6 scores or above. The incidence of adverse reactions was 100%. The most common adverse reactions were hematological events including leucopenia (70.4%, 19/27) and granulocytopenia (74.1%, 20/27). Non-hematological adverse events included fatigue (51.9%, 14/27) and oral mucositis (37.0%, 10/27). One patient was withdrawn due to grade 4 thrombocytopenia. Among 26 patients with feasible efficacy evaluation, 18 (69.2%) achieved partial remission, 3 (11.5%) achieved stable disease, and 5 (19.2%) disease progression. The objective remission rate was 69.2% (18/26) and the disease control rate was 80.8% (21/26). Fourteen patients underwent surgery, including 6 patients undergoing R0 resection with the R0 resection rate of 42.9% (6/14). The postoperative pathological response rate was 64.3% (9/14). The follow-up time was 12-40 months, and the follow-up rate was 100%. The 1-year OS rate was 65.2% and the survival time was (14.0±1.7) months. The 1-year OS rates of P1a/P1b group and P1c group were 81.8% and 42.0% respectively, whose difference was statistically significant (P=0.041). The 1-year OS rates of PCI 1-5 group and PCI ≥6 group were 67.3% and 38.5% respectively, whose difference was statistically significant (P=0.022). Conclusion: In the conversion treatment of gastric cancer peritoneal metastasis, the safety of apatinib combined with oxaliplatin and S-1 is acceptable, and this regimen shows a good short-term survival efficacy in patients with P1a/P1b and PCI of 1-5.

A multi-center retrospective study of perioperative chemotherapy for gastric cancer based on real-world data / 中华胃肠外科杂志

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

Efficacy of free superficial circumflex iliac artery flap combined with anterolateral thigh flap for repairing large skin defect of the hand / 中华创伤杂志

Objective:To investigate the clinical effect of free superficial circumflex iliac artery flap combined with anterolateral thigh flap in repairing large skin defect of the hand.Methods:A retrospective case series study was conducted to analyze the clinical data of 9 patients with large skin defect of the hand admitted to Ningbo No.6 Hospital from January 2016 to December 2019，including 7 males and 2 females，aged 31-63 years［（45.3±5.6）years］. The area of skin defect reanged from 20 cm×15 cm to 25 cm×20 cm. One side of the superficial circumflex iliac artery flap and the contralateral anterolateral thigh flap were used for repair. Both recipient and donor sites were sutured at the first stage. The ilioinguinal region and thigh donor region were sutured directly. The area of superficial circumflex iliac artery flap was from 19 cm×6 cm to 23 cm ×10 cm and that of anterolateral thigh flap was 19 cm×9 cm to 23 cm×8 cm. The flap survival，healing of donor and recipient area and complications were observed. At 1，6 and 12 months after operation，the function of the flap was evaluated by the late functional evaluation criteria of the flap，hand function by the upper limb functional evaluation criteria of the Chinese Medical Association，and scar condition of the donor site by Vancouver Scar Scale（VVS）. At the last follow-up，the color，elasticity，appearance and scar of the donor site were observed.Results:All patients were followed up for 6-18 months［（12.5±2.3）months］. All flaps survived successfully. All patients achieved donor-site healing at the first stage，except that one patient experienced incision dehiscence in the thigh donor site after operation and healed after the second stage suture. The texture and appearance of the flaps were good. The flap in 5 patients was obviously bloated. Therefore，the secondary skin flap repair was selected，and the appearance was significantly improved after operation. Scores for function of the flap and the hand were improved over time（ P<0.05）. At 12 months after operation，the function of the flap was excellent in 3 patients，good in 4 and fair in 2，with the excellent and good rate of 78%；the result of hand function was excellent in 3 patients，good in 3 and fair in 3，with the excellent and good rate of 67%. The VVS score of the donor site decreased from（9.7±1.3）points at postoperative 1 month to（5.7±0.9）points at postoperative 6 months and（3.4±0.8）points at postoperative 12 months（ P<0.05）. At the latest follow-up，the color and elasticity of the flap was similar to that of the surrounding skin tissue，only with slight bloating；the scar of the donor site was small. Conclusions:The free superficial circumflex iliac artery flap combined with anterolateral thigh flap can cover large skin defect of the hand at one time，with good appearance and texture of the flap. The appearance and function of the wounded hand are good after operation，leaving only linear scar in the donor site.

Understanding the Psychosocial Needs of Women who Present with Advanced Breast Cancer

INTRODUCTION@#Advanced breast cancer (ABC) remains common in Singapore. In 2019, 22.1% of breast cancer patients presented with ABC in our institution. Despite increasing affluence and the advent of national mammographic screening, the incidence of ABC has not changed significantly. This suggests inherent differences in women who present late. We aim to explore the socio-economic background, knowledge and attitudes of women who present with ABC.@*METHODS@#Between December 2013 and July 2015, 100 patients who presented consecutively with ABC in a tertiary institution in Singapore were recruited to participate in an interviewer-led questionnaire exploring psychosocial and economic issues.@*RESULTS@#Among the 100 patients, 63 and 37 presented with stages 3 and 4 breast cancer respectively. Median age was 57 (27-86), 52% had at least secondary education, 53% had no formal employment and 71% were married; 88% were aware of breast cancer symptoms, 82% were aware that mammography can help detect cancer, 82% believed that current treatment modality for breast cancer is effective, 96% had never undergone a mammography and 52.9% felt mammograms were unnecessary. A total of 64% presented symptomatic from the breast tumour, with a median duration of 3 months. Many of the patients were aware of breast cancer symptoms and the utility of mammography. However, a group of patients did not comply with screening. This may be due to poor understanding about breast screening and detection in its asymptomatic phase.@*CONCLUSION@#Further public education to improve understanding of breast cancer and screening mammography may help to improve rates for earlier detection of breast cancer.

All-ceramic premolar guiding plate retains resin-bonded fixed partial dentures / 华西口腔医学杂志

OBJECTIVE@#This study aims to investigate the fracture resistance and short-term restorative effects of resin-bonded fixed partial dentures (RBFPDs) made from heat-pressed lithium-disilicate-based glass-ceramic (IPS e.max press) and zirconia ceramic (WIELAND) and retained by all-ceramic guiding plates when used to restore missing mandibular second premolars.@*METHODS@#A total of 64 human mandibular first premolars and first molars were prepared as abutments, then were randomly divided into 4 groups (n=8): E0, heat-pressed ceramic RBFPDs, no cyclic loading; E1, heat-pressed ceramic RBFPDs exposed to 300 000 cycles of dynamic loading; W0, zirconia ceramic RBFPDs, no cyclic loading; and W1, zirconia ceramic RBFPDs exposed to 300 000 cycles of dynamic loading. Fracture strength was tested in a universal testing machine.@*RESULTS@#The medians of fracture strength were 1 242.85 N±260.11 N (E0), 1 650.85 N±206.77 N (W0), 1 062.60 N±179.98 N (E1), and 1 167.61 N±265.50 N (W1). Statistical analysis showed that all the groups exhibited significantly higher fracture strength compared with the maximum bite force in the premolar region (360 N; P0.05). Significant statistical differences were found between the zirconia ceramic groups (W0 and W1, P0.05) after dynamic loading.@*CONCLUSIONS@#The RBFPDs retained by all-ceramic guiding plates exhibited promising fracture properties and optimal short-term restorative effects when used to restore missing mandibular second premolars.

Tiaoxin Recipe, a Chinese herbal formula, inhibits microRNA-34a expression in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease / 中西医结合学报

OBJECTIVE@#To investigate the effect and underlying mechanisms of Tiaoxin Recipe (a Chinese herbal formula) treatment on Alzheimer's disease (AD).@*METHODS@#Twelve-week-old APPswe/PS1ΔE9 (APP/PS1) double transgenic mice were used as a model of AD-afflicted mice. One group of mice was treated with Tiaoxin Recipe by gastrogavage for 12 weeks, while two other groups were given intraperitoneal injections of nicotinamide adenine dinucleotide or FK866 for 4 weeks. Morris water maze and thioflavin S staining tests were performed to evaluate cognitive impairment and amyloid plaque deposition, respectively. Serum amyloid-β1-42 (Aβ1-42) content was detected using an enzyme-linked immunosorbent assay, and quantitative reverse transcription-polymerase chain reaction was performed to examine the expression levels of microRNA-34a (miR-34a) in cortex and hippocampus samples of the study mice.@*RESULTS@#Compared with the normal control group, the memory and learning abilities of the APP/PS1 model group were found to be impaired (P < 0.01), as shown by the increased levels of senile plaque deposition in cortex and hippocampus (P < 0.01), miR-34a expression (P < 0.01) and serum Aβ1-42 content (P < 0.01). Treatment with Tiaoxin Recipe significantly reduced memory impairment (P < 0.01) by reducing amyloid plaque accumulation in cortex and hippocampus (P < 0.01), miR-34a expression (P < 0.01) and serum Aβ1-42 content (P < 0.01) in APP/PS1 mice.@*CONCLUSION@#Tiaoxin Recipe is a viable complementary or alternative therapeutic treatment that is capable of delaying the development of early-stage AD by inhibiting the expression of miR-34a.

Predictive genes for pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer / 医学研究生学报

Objective Only 10%-30% of locally advanced rectal cancer (LARC) respond pathologically to neoadjuvant chemoradiotherapy (NCRT). This study was to search for a feasible gene signature predicting pathological response to NCRT in LARC. Methods Four datasets GSE35452, GSE46862, GSE68204 and GSE53781 relating to the mRNA expression matrix and tumor regression grading of LARC after NCRT were obtained from the Gene Expression Omnibus. The first three datasets were merged into one and divided into training sets (n = 121) and internal validation sets (n = 53) after batch effect removal, and the last dataset was used as external validation sets (n = 26). Pathological response-related genes in the training sets were identified by univariate logistic regression and t-test (crude P < 0.05) and ranked by the P-value. All the genes with P < 0.05 were subjected to the least absolute shrinkage and selection operator (LASSO) and the first 50 to the support vector machine algorithm (SVM) for the establishment of predicting models, followed by verification in the corresponding validation set. Random sampling was repeated 500 times to determine the stability of the selected gene signatures and models. With the 21 most important genes revealed by LASSO as the candidates for model construction, the sensitivity index for NCRT was calculated as the total sum of coefficients in logistic regression and expression values in the merged datasets and external validation sets. The differentially expressed genes were identified between the response and non-response groups in the 174 merged datasets and subjected to regulatory network analysis. Results A total of 12 803 genes from the GSE35452, GSE46862 and GSE68204 datasets were included in the analysis. The accuracy, specificity and sensitivity of LASSO for predicting the pathological response in the internal validation sets were 0.523 (95% CI: 0.396-0.642, 0.578 (95% CI: 0.373-0.762) and 0.464 (95% CI: 0.258-0.700), while those of SVM were 0.504 (95% CI: 0.377-0.623), 0.596 (95% CI: 0.393-0.830) and 0.405(95% CI: 0.182-0.650), respectively. The area under the ROC curve (AUC) for pathological response prediction was 0.863 (95% CI: 0.811-0.912) in the 174 merged datasets and 0.925 (95% CI: 0.817-1.000) in the external validation sets. Conclusion The model for predicting response to NCRT established using the expression of candidate genes identified from a specific set of patients has a frustratingly low capacity in an independent set, probably because of high tumor heterogeneity among different individuals. Regulatory network analysis indicates that radiotherapy-resistance in rectal cancer may be mediated by the mechanisms underlying the invasion, metastasis and transformation of the malignancy.