Survival analysis of 6 737 surgically resected gastric cancer cases in China from a large single institution hospital-based cancer registry database / 中国癌症杂志

Background and purpose:Follow-up data of 6 737 patients undergoing surgery for gastric cancer were collected based on hospital registration,and the 1-,3-and 5-years observed overall survival(OS)rates and disease-free survival(DFS)rates were analyzed to provide real-world research evidence for the prevention and control of gastric cancer and policy making in China.Methods:A total of 6 737 gastric cancer patients who underwent surgical treatment at Fudan University Shanghai Cancer center from 2015 to 2020 were included in this study.Clinical information and the follow-up endpoint data were collected through medical records review,telephone visits and death registry data linkage.The last follow-up date was November 30,2023.Kaplan-Meier method was applied in evaluating the 1-,3-and 5-year OS rate and DFS rate,and survival data were described by different subgroups including age group,gender,treatment period,tumor staging,and pathological characteristics.Results:With a median follow-up time of 50.99 months,the 5-year OS rate of surgically resected gastric cancer patients was 70.37%,and 5-year DFS rate in Ⅰ-Ⅲ stage cases was 69.46%.The 5-year OS rates of stage Ⅰ,Ⅱ,Ⅲ and Ⅳ were 94.32%,82.56%,51.01%and 23.97%,respectively.The differences in survival among patients with different age,tumor location,gross classification,Borrmann classification and Laurence classification were significant.Conclusion:Staging is an important factor directly affecting the survival of gastric cancer patients.Screening and early diagnosis and treatment in large population,especially high-risk group,should be strengthened to further improve the patients'survival.

Clinicopathological analysis of pseudostratified ependymal tubules in ovarian mature teratoma / 中华病理学杂志

Objective: To investigate the morphology and immunohistochemical (IHC) expression of pseudostratified ependymal tubules in ovarian mature teratoma (MT). Methods: Five cases of ovarian MT with pseudostratified ependymal tubules were collected from Shenzhen Hospital(Futian) of Guangzhou University of Chinese Medicine and the Eighth Affiliated Hospital of Sun Yat-sen University from March 2019 to March 2022. In addition, 15 cases of ovarian MT with monolayer ependymal epithelium from Shenzhen Hospital (Futian) of Guangzhou University of Chinese medicine and seven cases of immature teratoma (IMT) from Hainan Provincial People's Hospital from March 2019 to March 2022 were collected as control. The morphologic characteristics and immunophenotypes of pseudostratified ependymal tubules, monolayer ependymal epithelium, and primitive neural epithelial tubules were observed and compared by H&E stain and IHC expression pattern of genes related to the differentiation status of neuroepithelium, namely SALL4, Glypican3, nestin, SOX2, Foxj1, and Ki-67. Results: Mean age of the five patients of ovarian MT with pseudostratified ependymal tubules was 26 years (range from 19 to 31 years). Two tumors were located in the left ovary and three in the right. All five cases were excised, and clinical follow-up was available (mean follow-up 1.5 years; range 0.5 to 3 years). No recurrence was noted in any cases. The pseudostratified ependymal tubules of ovarian MT, which were lined with columnar or oval epithelia up to 4-6 layers, were morphologically similar to the primitive neuroepithelial tubules of IMT and different from monolayer ependymal epithelium of ovarian MT. By immunohistochemistry, SALL4 and Glypican3 were negative, Foxj1 was positive and Ki-67 index was lower in the pseudostratified ependymal tubules and the monolayer ependymal epithelium of ovarian MT. However, the primitive neuroepithelial tubules of IMT showed variably expression of SALL4 and Glypican3, were negative for Foxj1 and high Ki-67 index. All the above three groups expressed nestin and SOX2. Conclusions: The pseudostratified ependymal tubules of ovarian MT, which have morphological similarities to the primitive neuroepithelial tubules of IMT, are similar to the monolayer ependymal epithelia of the MT in immunophenotype. IHC assessment of Foxj1 and Ki-67 is helpful to differentiate the pseudostratified ependymal tubules of ovarian MT from the primitive neuroepithelial tubules of IMT.

Dichotomous cis-regulatory motifs mediate the maturation of the neuromuscular junction by retrograde BMP signaling.

Retrograde bone morphogenetic protein (BMP) signaling at the Drosophila neuromuscular junction (NMJ) has served as a paradigm to study TGF-ß-dependent synaptic function and maturation. Yet, how retrograde BMP signaling transcriptionally regulates these functions remains unresolved. Here, we uncover a gene network, enriched for neurotransmission-related genes, that is controlled by retrograde BMP signaling in motor neurons through two Smad-binding cis-regulatory motifs, the BMP-activating (BMP-AE) and silencer (BMP-SE) elements. Unpredictably, both motifs mediate direct gene activation, with no involvement of the BMP derepression pathway regulators Schnurri and Brinker. Genome editing of candidate BMP-SE and BMP-AE within the locus of the active zone gene bruchpilot, and a novel Ly6 gene witty, demonstrated the role of these motifs in upregulating genes required for the maturation of pre- and post-synaptic NMJ compartments. Our findings uncover how Smad-dependent transcriptional mechanisms specific to motor neurons directly orchestrate a gene network required for synaptic maturation by retrograde BMP signaling.

Patients with benign breast disease and breast cancer need more COVID-19 vaccines

Albeit the efficacy of COVID-19 vaccines in immunocompromised patients is undermined, it is still found beneficial. Patients with cancer have a much lower COVID-19 vaccination rate globally, and the vaccination coverage in breast cancer patients in China remains elusive. A total of 23029 patients with benign breast diseases and breast cancers were included in the study, and the vaccination rates of patients with benign breast tumors and other benign breast diseases, nonmetastatic and metastatic breast cancer were 44.0%, 54.7%, 19.2% and 9.6%, respectively. Breast cancer in situ patients had a similar vaccination rate with patients with benign breast tumors (45.9% vs 44.0%) while those with invasive breast cancer had much lower vaccination rates. The overall vaccination rate remains meager in breast cancer patients, and gap was found in patients with lower clinical stage. Hence vaccination should be further promoted among patients with benign breast diseases and breast cancer.

Review of taste masking techniques in Chinese patent medicine / 中国中药杂志

Single herbs and Chinese patent medicine preparations often have bad taste, such as bitterness and astringency, which is one of the key factors affecting patients' medication compliance, and would affect the therapeutic effect and restrict the extensive application in clinical practice. Therefore, how to make use of taste masking techniques to improve the bad taste of traditional Chinese medicines has become an important project. Through the collection and summarization of Chinese and foreign journals and papers in recent years, this paper discussed the generation mechanism of bitter taste, the new methods of masking bitter taste and the evaluation me-thods of bitter taste, in order to provide references for the taste masking of Chinese patent medicines preparations.

A low affinity cis-regulatory BMP response element restricts target gene activation to subsets of Drosophila neurons.

Retrograde BMP signaling and canonical pMad/Medea-mediated transcription regulate diverse target genes across subsets of Drosophila efferent neurons, to differentiate neuropeptidergic neurons and promote motor neuron terminal maturation. How a common BMP signal regulates diverse target genes across many neuronal subsets remains largely unresolved, although available evidence implicates subset-specific transcription factor codes rather than differences in BMP signaling. Here we examine the cis-regulatory mechanisms restricting BMP-induced FMRFa neuropeptide expression to Tv4-neurons. We find that pMad/Medea bind at an atypical, low affinity motif in the FMRFa enhancer. Converting this motif to high affinity caused ectopic enhancer activity and eliminated Tv4-neuron expression. In silico searches identified additional motif instances functional in other efferent neurons, implicating broader functions for this motif in BMP-dependent enhancer activity. Thus, differential interpretation of a common BMP signal, conferred by low affinity pMad/Medea binding motifs, can contribute to the specification of BMP target genes in efferent neuron subsets.

A single-center retrospective study on influence factors on surgical methods in DCIS patients / 中华内分泌外科杂志

Objective To evaluate the influence factors on surgical methods in DCIS (Ductal carcinoma in situ) patients,and the prognosis of different surgical methods in a 10-year single-center retrospective study.Methods We retrospectively included 1557 DCIS patients who received treatments in our center from Jan.2006 to Nov.2016.T tests,Chi-square analysis and logistic regression analysis were used to analyze influence factors on surgical methods.Kaplan-Meier and Log-rank analysis were used to evaluate recurrence-free survival(RFS) and loco-regional recurrence-free survival (LRRFS) in patients with different surgical methods.Results Of the enrolled 1557 DCIS patients,surgical methods included modified radical mastectomy,simple mastectomy (with or without axillary evaluation) and breast conservation surgery (with or without axillary evaluation).The number of DCIS cases in our center increased (P＜0.001),so did the percentage of DCIS in annual malignant surgery cases (P=-0.026).Significant decrease was found in modified radical mastectomy (P=0.012).More than half of the patients received simple mastectomy after 2010,and more than one fifth of the patients received breast conservation surgery after 2008.About 13.99％ patients who received mastectomy had breast reconstruction.The independent influence factors of refusing breast conservation surgery were age ≥ 50(P＜0.001),medium nuclear grade (P=0.044),tumor size ＞ 15mm (P＜0.001) and spontaneous discharge (P＜0.001).Patients with smaller tumor size (≤ 15mm) and no spontaneous discharge had 4.18-fold and 7.04-fold greater preference for breast conservation surgery,respectively(OR=0.232,P＜0.001;OR=0.144,P＜0.001).There were no significant differences in RFS and LRRFS in patients with different surgical methods.Conclusion The evaluation in trends and influence factors of different surgical methods provides basis on surgical precision medicine in DCIS patients.

A single-center retrospective study on axillary evaluation in 1 557 breast ductal carcinoma in situ patients between 2006 and 2016 / 中华外科杂志

Objectives@#To examine the influence factors on axillary evaluation in ductal carcinoma in situ (DCIS) patients, and the prognosis of different choices of axillary evaluation in a single-center retrospective study.@*Methods@#Totally 1 557 DCIS patients admitted in Department of Breast Surgery, Fudan University Shanghai Cancer Center from January 2006 to November 2016 were retrospectively enrolled. All patients were female. The median age was 49 years (range: 21 to 85 years). Surgical methods included modified radical mastectomy, simple mastectomy (with or without axillary evaluation) and breast conservation surgery (with or without axillary evaluation). Axillary evaluation included axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB). T tests, χ2 test and Logistic regression analysis was used to analyze influence factors on axillary evaluation, respectively. Kaplan-Meier curve and Log-rank analysis were used to evaluate recurrence-free survival (RFS) and loco-regional recurrence-free survival (LRRFS) in patients with different surgical methods.@*Results@#Among the 1 557 DCIS patients, there were 1 226 cases received axillary evaluation, while 331 cases not received axillary evaluation. Patients were separated into 3 groups by different axillary evaluation choices: SLNB group (957 cases, 61.46%), ALND group (197 cases, 12.65%) and no evaluation group (403 cases, 25.88%). The patients in SLNB group increased significantly (P=0.000), from 3.85% (60/1 557) in 2006 to 75.19% (1 170/1 557) in 2016. The independent influence factors of receiving axillary evaluation were high nuclear grade (OR=3.191, 95%CI: 1.722 to 5.912, P=0.001) and tumor size>15 mm (OR=1.698, 95%CI: 1.120 to 2.573, P=0.012). Also, patients received breast conservation surgery were more likely to refuse axillary evaluation (OR=0.155, 95%CI: 0.103 to 0.233, P=0.000). There were no significant differences in RFS and LRRFS in patients with different axillary evaluation choices.@*Conclusions@#The investigation in trends and influence factors of different axillary evaluation choices provided basis on surgical precision medicine in DCIS patients. Patients received SLNB increased significantly. The independent influence factors of axillary evaluation were nuclear grade, tumor size and surgical methods. There was no significant differences in prognosis among the groups receiving different axillary evaluations.

Comparison of modeling effects of two different 7, 12-dimethylbenza anthracene induced breast cancer models in tree shrew / 中华肿瘤杂志

Objective@#To explore the feasibility of 7, 12-dimethylbenz[a] anthracene (DMBA) induced tree shrew breast cancer model, and compare the effects of two administration modes by gavage and mammary gland injection.@*Methods@#A total of 40 tree shrews were randomly divided into two groups (20 animals per group): DMBA gavage group and mammary gland injection group. DMBA was dissolved in edible vegetable oil. For gavage group, tree shrews were administered with DMBA solutions (15 mg/kg) by gavage once a day. For mammary gland injection group, DMBA solution (10 mg/kg) was injected into the mammary fat pad of tree shrews, and the injection was performed for a total of 3 times. From the first administration of DMBA, medroxyprogesterone acetate (MPA, 100 mg/kg) was intramuscularly injected into the muscles of the lateral thighs of tree shrews at the same time, for a total of 5 times. The tumorigenesis and survival of tree shrews were monitored. The tumor histological morphology was observed by HE staining. The expression of estrogen receptor (ER), progesterone receptor (PR), cytokeratin5/6 (CK5/6) and human epidermal factor receptor-2 (HER-2) was detected by immunohistochemical staining.@*Results@#In the gavage group, there were 10 deaths, and 4 tree shrews developed mammary tumors with 20.0% (4/20) tumor formation rate. The success rate of mammary cancer modeling was 10.0% (2/20), and the tumor formation time was 197.3±15.1 days. In the mammary gland injection group, there were 8 tree shrews died, and 9 tree shrews formed tumors with 45.0% (9/20) tumor formation rate. The success rate of mammary cancer modeling was 40.0% (8/20), and the tumor formation time was 71.8±19.0 days. There was no significant difference in mortality and tumor formation rate (P>0.05) between the two groups (all P>0.05). However, in the mammary gland injection group, the success rate of mammary cancer modeling was significantly higher than that in the gavage group (P<0.05), whereas the tumor formation time was markedly shorter than that in the gavage group (P<0.01). The pathological types in the gavage group included ductal hyperplasia, intraductal papilloma and ductal carcinoma in situ, while those in the breast injection group included intraductal papilloma and ductal carcinoma in situ. In both groups, immunohistochemical staining showed the negative expression of HER-2 but positive expression of ER, PR and CK5/6 with varying degrees.@*Conclusion@#Both the DMBA gavage and mammary gland injection can successfully establish the tree shrew breast cancer model, and the modeling effect of mammary gland injection is better than gavage.

Remote Ischemic Postconditioning for Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials / 中华医学杂志(英文版)

<p><b>Background</b>Remote ischemic postconditioning (RIPostC) appears to protect distant organs from ischemia-reperfusion injury (IRI). However, cerebral protection results have remained inconclusive. In the present study, a meta-analysis was performed to compare stroke patients with and without RIPostC.</p><p><b>Methods</b>CNKI, WanFang, VIP, CBM, PubMed, and Cochrane Library databases were searched up to July 2016. Data were analyzed using both fixed-effects and random-effects models by Review Manager. For each outcome, risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) were calculated.</p><p><b>Results</b>A total of 13 randomized controlled trials that enrolled a total of 794 study participants who suffered from or are at risk for brain IRI were selected. Compared with controls, RIPostC significantly reduced the recurrence of stroke or transient ischemic attacks (RR = 0.37; 95% CI: 0.26-0.55; P < 0.00001). Moreover, it can reduce the levels of the National Institutes of Health Stroke Scale score (MD: 1.96; 95% CI: 2.18-1.75; P < 0.00001), modified Rankin Scale score (MD: 0.73; 95% CI: 1.20-0.25; P = 0.00300), and high-sensitivity C-reactive protein (MD: 4.17; 95% CI: 4.71-3.62; P < 0.00001) between the two groups. There was no side effect of RIPostC using tourniquet cuff around the limb on ischemic stroke treating based on different intervention duration.</p><p><b>Conclusion</b>The present meta-analysis suggests that RIPostC might offer cerebral protection for stroke patients suffering from or are at risk of brain IRI.</p>

Cost-effectiveness of multiple screening modalities on breast cancer in Chinese women from Shanghai / 中华流行病学杂志

Objective To determine the most cost-effective modality for breast cancer screening in women living in Shanghai.Methods A Markov model for breast cancer was redeveloped based on true effect which was derived from a project for detection of women at high risk of breast cancer and an organized breast cancer screening program conducted simultaneously in Minhang district,Shanghai,during 2008 to 2012.Parameters of the model were derived from literatures.General principles related to cost-effectiveness analysis were used to compare the costs and effects of 12 different screening modalities in a simulated cohort involving 100 000 women aged 45 years.Incremental cost-effectiveness ratio (ICER) was used to determine the most cost-effective modality.Sensitivity analysis was conducted to evaluate how these factors affected the estimated cost-effectiveness.Results The modality of biennial CBE followed by ultrasonic and mammography among those with positive CBE was observed as the most cost-effective one.The costs appeared as 182 526 Yuan RMB per life year gained and 144 386 Yuan RMB per quality adjusted life-year (QALY) saved,which were within the threshold of 2-3 times of local per capita Gross Domestic Product.Results from sensitivity analysis showed that,due to higher incidence rate of breast cancer in Shanghai,the cost per QALY would be 64 836 Yuan RMB lower in Shanghai than the average level in China.Conclusion Our research findings showed that the biennial CBE program followed by ultrasonic and mammography for those with positive CBE results might serve as the optimal breast cancer screening modality for Chinese women living in Shanghai,and thus be widely promoted in this population elsewhere.

Cost-effectiveness of multiple screening modalities on breast cancer in Chinese women from Shanghai / 中华流行病学杂志

Objective To determine the most cost-effective modality for breast cancer screening in women living in Shanghai.Methods A Markov model for breast cancer was redeveloped based on true effect which was derived from a project for detection of women at high risk of breast cancer and an organized breast cancer screening program conducted simultaneously in Minhang district,Shanghai,during 2008 to 2012.Parameters of the model were derived from literatures.General principles related to cost-effectiveness analysis were used to compare the costs and effects of 12 different screening modalities in a simulated cohort involving 100 000 women aged 45 years.Incremental cost-effectiveness ratio (ICER) was used to determine the most cost-effective modality.Sensitivity analysis was conducted to evaluate how these factors affected the estimated cost-effectiveness.Results The modality of biennial CBE followed by ultrasonic and mammography among those with positive CBE was observed as the most cost-effective one.The costs appeared as 182 526 Yuan RMB per life year gained and 144 386 Yuan RMB per quality adjusted life-year (QALY) saved,which were within the threshold of 2-3 times of local per capita Gross Domestic Product.Results from sensitivity analysis showed that,due to higher incidence rate of breast cancer in Shanghai,the cost per QALY would be 64 836 Yuan RMB lower in Shanghai than the average level in China.Conclusion Our research findings showed that the biennial CBE program followed by ultrasonic and mammography for those with positive CBE results might serve as the optimal breast cancer screening modality for Chinese women living in Shanghai,and thus be widely promoted in this population elsewhere.

Cost-effectiveness analysis of two breast cancer screening modalities in Shanghai, China / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the cost-effectiveness of two breast cancer screening modalities conducted in Minhang district of Shanghai, China.</p><p><b>METHODS</b>An organized and an opportunistic breast screening programs were implemented among women aged 35-74 years in Minhang district of Shanghai between May 2008 and Oct 2010, and were compared with the results obtained without screening. Costs related to screening were obtained by access to finance data of the screening programs, and costs of first treatment were collected through patient survey and medical reimbursement system query. Information on breast cancer stage was obtained from Shanghai Cancer Registry and confirmed by medical chart review. The effectiveness of screening was evaluated by breast cancer stage improvement.Cost-effectiveness ratios (CERs) were computed as costs of gaining a stage improvement from a specified screening strategy when compared with the results obtained without screening. Incremental cost-effectiveness (ICER) which compares the two screening strategies was calculated by dividing the difference in total net costs and the difference in stages improved between the two screening strategies.</p><p><b>RESULTS</b>Thirty-five, one hundred and ninety-three and four hundred and seventy-nine breast cancer cases were identified in the organized screening, opportunistic screening and control groups, with an early detection rate of 46.9%, 40.7% and 38.9%, respectively. The costs of screening were 208 yuan per person or 72 453 yuan per case detected in the organized screening group and were 21 yuan per person or 11 640 yuan per case detected in the opportunistic screening group. The total cost was 103 650 yuan per case in the organized screening group, significantly higher than 50 712 yuan in the opportunistic screening group and 35 413 yuan in the control group. However, the average direct medical cost was significantly lower in the organized screening group than that in the opportunistic screening group and control group, with median costs of 11 024 yuan, 13 465 yuan and 14 243 yuan per case, respectively (P<0.001). The additional cost per case detected was 68 237 yuan for the organized screening and 15 299 yuan for opportunistic screening. The CERs were 135 291 yuan and 152 179 yuan per stage improved in the organized screening and opportunistic screening relative to the control group, with ICER of organized versus opportunistic screening being 131 086 yuan per stage improved.</p><p><b>CONCLUSIONS</b>The organized screening modality and the opportunistic one are both effective in early detecting breast cancer in Chinese women. The organized screening costs more than opportunistic screening, but with a better cost-effectiveness. It may be used as an option in economically developed areas of China.</p>

Overexpression of P53 is prognostic for aromatase inhibitor resistance in early stage postmenopausal patients with ER-positive breast cancer / 中国癌症杂志

Background and purpose:Tumor suppressor gene P53 has long been studied in tumors, including breast cancer. More studies focused on the relationship between P53 and prognosis of breast cancer and found that P53 overexpression suggested a bad prognosis. However, the effect of P53 on early stage postmenopausal patients with ER-positive breast cancer has not been clariifed yet. This study was to investigate the role of P53 plays in aromatase inhibitor (AI) resistance among early stage postmenopausal patients with ER-positive breast cancer patients. Methods:A total number of 293 operable breast cancer patients who received surgical treatment during Jul. 2000 to Jul. 2006 in Fudan University Shanghai Cancer Center were enrolled into this study. All patients received AI treatment. The SPSS 12.0 software was used to estimate the survival rate. Univariate and multivariate analysis were also performed via above software. Results:The median follow-up time is 72 months (6-140 months). The 5 year disease free survival (DFS) of P53 positive and negative were 78%and 89%. The results showed that P53 overexpression (HR=1.729, 95%CI:1.038-2.880, P=0.035), pathological stage (HR=2.270, 95%CI:1.399-3.681, P=0.001);histological grade (HR=2.328, 95%CI:1.312-4.133, P=0.004); age (HR=1.988, 95%CI:1.511-2.617, P<0.005) were still the independent risk factors of recurrence and metastasis in breast cancer patients treated with AI. Conclusion:P53 overexpression correlated strongly with AI resistance in early stage postmenopausal patients with ER-positive breast cancer patients who were treated with AI and conifrmed the relevance of previously described prognostic factors. It is reasonable to take P53 expression into account when we evaluate the risk of breast cancer patients and decide the anti-cancer treatment strategy.