[Clinical outcome of combined over-the-top reconstruction with modified Lemaire procedure in one-stage revision anterior cruciate ligament reconstruction].

Objective: To investigate the clinical effect of over-the-top (OTT) reconstruction of the anterior cruciate ligament (ACL) combined with the modified Lemaire technique in one-stage ACL revision. Methods: It's a retrospective study. The clinical data of 37 patients who underwent one-stage revision of ACL using OTT combined with modified Lemaire technique from April 2020 to May 2023 in the Department of Sports Medicine of Xinhua Hospital Affiliated to Dalian University were retrospectively analyzed. There were 28 males and 9 females with a mean age of (32.7±5.7) years. The postoperative knee function and surgical revision effect were evaluated by subjective and objective evaluation indexes of the knee joint before and 3 months and 24 months after surgery. The subjective evaluation indexes included the International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner score; and the objective evaluation indexes included the anterior-posterior static displacement distance of the tibia, tibia-femur relative rotation angle, the Lachman test, the axial shift test, and the ratio of the loss of muscle strength of the lower limb. Results: At the final follow-up, all patients returned to pre-injury motor level, with significant improvements in IKDC scores (45.3±6.8 preoperatively, 67.5±4.7 and 93.2±2.3 at 3 months and 2 years after the operation, respectively), Lysholm scores (57.2±2.6 preoperatively, 72.6±2.9 and 89.7±3.7 at 3 months and 2 years after the operation, respectively), and Tegner scores (3.1±0.7 preoperatively, 4.9±0.6 and 5.8±1.3 at 3 months and 2 years after the operation, respectively) (all P<0.001). The anterior-posterior static displacement distance of the tibia reduced significantly [from (5.2±0.5) mm before the operation to (1.4±0.5) mm at 2 years postoperatively) (P<0.001)]; and the relative rotation angle of the tibia-femur restored to the normal physiological range, it was reduced from 6.2°±1.2° before the operation to 1.7°±0.3° 2 years after (P<0.001). The Lachman test and axial shift test at 2 years postoperatively were all negative. The muscle strength loss ratio of the affected lower limb was significantly better than that before the operation (P<0.001). Conclusion: The use of OTT reconstruction combined with modified Lemaire technique for revision of ACL in patients with ACL reconstruction failure can circumvent the tunnel problem for one-stage revision and better restore the stability and function of the knee joint, with ideal clinical results.

[Interpretation of specification for service of cancer screening for workers].

As the backbone force of China's social and economic construction, the health status of workers is closely related to the nation's productivity and social development. Currently, cancers have become one of the major diseases threatening the health of workers. However, there are still many shortcomings in the cancer screening services for the workers. To standardize cancer screening services for workers, ensure the quality of screening services, and improve the overall screening effectiveness, 19 institutions, including Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, have jointly formulated the Group Standard "Specification for service of cancer screening for workers (T/CHAA 023-2023)". This standard follows the principles of "legality, scientific rigor, advancement, and feasibility" and combines the frontier scientific advances in cancer screening. It clarifies the relevant requirements for service principles, service design, service delivery, service management, service evaluation, and improving worker cancer screening. Implementing this group standard will help connect the common screening needs of workers, employers, and cancer screening service providers, standardize the screening process, improve screening quality, and ultimately increase the early diagnosis rate and survival rate of cancer patients. Consequently, this group standard will help safeguard workers' health rights and interests, ensure the labor force resources, promote the comprehensive coordinated and sustainable development of society, and contribute to realizing the "Healthy China 2030" strategic policy.

MRI-based radiomics model to preoperatively predict mesenchymal transition subtype in high-grade serous ovarian cancer.

AIM: To develop a magnetic resonance imaging (MRI)-based radiomics model for the preoperative identification of mesenchymal transition (MT) subtype in high-grade serous ovarian cancer (HGSOC). MATERIALS AND METHODS: One hundred and eighty-nine patients with histopathologically confirmed HGSOC were enrolled retrospectively. Among the included patients, 55 patients were determined as the MT subtype and the remaining 134 were non-MT subtype. After extracting a total of 204 features from T2-weighted imaging (T2WI) and contrast-enhanced (CE)-T1WI images, the Mann-Whitney U-test, Spearman correlation test, and Boruta algorithm were adopted to select the optimal feature set. Three classifiers, including logistic regression (LR), support vector machine (SVM), and random forest (RF), were trained to develop radiomics models. The performance of established models was evaluated from three aspects: discrimination, calibration, and clinical utility. RESULTS: Seven radiomics features relevant to MT subtypes were selected to build the radiomics models. The model based on the RF algorithm showed the best performance in predicting MT subtype, with areas under the curves (AUCs) of 0.866 (95 % confidence interval [CI]: 0.797-0.936) and 0.852 (95 % CI: 0.736-0.967) in the training and testing cohorts, respectively. The calibration curves, supported with Brier scores, indicated very good consistency between observation and prediction. Decision curve analysis (DCA) showed that the RF-based model could provide more net benefit, which suggested favorable utility in clinical application. CONCLUSION: The RF-based radiomics model provided accurate identification of MT from the non-MT subtype and may help facilitate personalised management of HGSOC.

A nomogram predicting the outcome of gallbladder cancer patients with different target organ metastases.

OBJECTIVE: Gallbladder cancer (GBC) is a highly aggressive malignancy that is associated with a high mortality rate globally. Unfortunately, distant metastases are often detected at the time of diagnosis. Therefore, we investigated the survival outcomes of gallbladder cancer patients with different metastases targeting organs, analyzed their prognosis, and explored their hidden clinical value. PATIENTS AND METHODS: Through data screening, a total of 398 patients with GBC with different target organ metastases were analyzed retrospectively, including patients with solitary bone metastasis, solitary liver metastasis, solitary lung metastasis, and multiple organ metastases. The survival results of different variables were plotted as Kaplan-Meier survival curves. Univariate and multivariate Cox regression models were used to screen study variables and identify independent prognostic factors. Finally, a nomogram was established to systematically evaluate the prognosis of patients with multiple organ metastasis. RESULTS: In the patient cohort, thirteen (3.3%) had solitary bone metastasis, 290 (72.9%) had solitary liver metastasis, 22 (5.5%) had solitary lung metastasis, and 73 (18.3%) had multiple organ metastases (including liver, lung, bone and brain metastases). Multivariate Cox analysis showed that the overall survival (OS) of patients with solitary lung metastasis was significantly better than that of patients with other organ metastasis (p = 0.038), while the difference in tumor cancer-specific survival (CSS) of this factor was not statistically significant (p > 0.05). Surgery and chemotherapy were independent prognostic protective factors for OS and CSS. The OS-related models exhibited a C-index of 0.74 (95% CI: 0.71-0.77), while the CSS-related models showed a slightly lower C-index of 0.73 (0.70-0.76). Both the OS- and CSS-related clinical prediction models had good accuracy. CONCLUSIONS: This study shows that different target organ metastases may affect the OS of patients with distant metastatic GBC. Patients receiving palliative surgery, primary site resection, radical surgery, and chemotherapy have significant survival benefits in terms of OS and CSS.

[A decade's review for membrane anatomy: the setting,events in it, order formed by primary fascia and serous membrane].

The successful report of total mesorectal excision (TME)/complete mesocolic excision (CME) has encouraged people to apply this concept beyond colorectal surgery. However, the negative results of the JCOG1001 trial denied the effect of complete resection of the "mesogastrium" including the greater omentum on the oncological survival of gastric cancer patients. People even believe that the mesentery is unique in the intestine, because they have a vague understanding of the structure of the mesentery. The discovery of proximal segment of the dorsal mesogastrium (PSDM) proved that the greater omentum is not the mesogastrium, and further revised the structure (definition) of the mesentery and revealed its container characteristics, i.e. the mesentery is an envelope-like structure, which is formed by the primary fascia (and serosa) that enclose the tissue/organ/system and its feeding structures, leading to and suspended on the posterior wall of the body. Breakdown of this structure leads to the simultaneous reduction of surgical and oncological effects of surgery. People quickly realized the universality of this structure and causality which cannot be matched by the existing theories of organ anatomy and vascular anatomy, so a new theory and surgical map- membrane anatomy began to form, which led to radical surgery upgraded from histological en bloc resection to anatomic en bloc resection.

[Development of membrane anatomy theory in gastric cancer surgery].

In the past decade, the concept of membrane anatomy has been gradually applied in gastric cancer surgery. Based on this theory, D2 lymphadenectomy plus complete mesogastric excision (D2+CME) has been proposed, which has been demonstrated to significantly reduce intraoperative bleeding and intraperitoneal free cancer cells during surgery, decrease surgical complications, and improve survival. These results indicate that membrane anatomy is feasible and efficacious in gastric cancer surgery. In this review, we will describe the important contents of membrane anatomy, including "Metastasis V"(2013, 2015), proximal segmentation of dorsal mesogastrium (2015), D2+CME procedure (2016), "cancer leak"(2018), and surgical outcomes of D2+CME (2022).

[Efficiency and safety analysis of Plerixafor combined with granulocyte colony-stimulating factor on autologous hematopoietic stem cell mobilization in lymphoma].

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.

[Atezolizumab therapy in Chinese patients with locally advanced or metastatic solid tumors: An open-label, phase â study].

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION: Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.

[Effect evaluation of the primary screening strategy for liver cancer in rural areas of China].

Objective: To estimate the effectiveness of the primary screening strategy for liver cancer in rural areas to provide basic information for the optimization and perfection of the technical program for the early detection and treatment of liver cancer. Methods: Residents including males aged 35-64 and females aged 45-64 from 9 counties in rural China between 2013 and 2015 were selected as the target population. The participant was classified into a high-risk and non-high-risk group based on the standardized questionnaire or HBsAg, and the Chi-squared test was applied to compare differences between the two groups. The Cox proportional hazard regression models were applied to assess hazard ratio (HR) and its 95% confidence interval (CI). Results: 358 348 participants were recruited from 2013 to 2015. 1 196 individuals were identified with liver cancer until December 31, 2021, with an incidence density of 52.0/10(5) person-years. Of the participants, 54 650 were assessed as high risk (15.3%) based on the questionnaire and the status of HBsAg. The high-risk population had a higher incidence density (168.3/10(5) person-years vs 31.5/10(5) person-years) and higher risk of developing liver cancer (HR=2.98, 95% CI=2.64-3.35), compared to the non-high-risk group. Based on the questionnaire-based high-risk assessment system, 47 884 (13.4%) individuals were identified as high risk, who showed statistical differences in terms of incidence density and incidence risk, in comparison to the low-risk population (all P<0.05). HBsAg can screen out a higher proportion of high-risk individuals who are women, non-smokers, non-drinkers, and individuals without a family history of liver cancer (all P<0.05). The sensitivity analysis of the effectiveness of the whole primary screening method is stable, and high-risk individuals still had a higher risk of liver cancer. Conclusions: The primary screening method of the questionnaire-based risk assessment system and HBsAg can achieve satisfactory effectiveness. The questionnaire-based risk assessment system could identify high-risk individuals to some extent, however, it still needs to be improved to meet the actual requirements.

[Gut microbiota and immune-related diseases].

There are direct and indirect interactions between gut microbiota and host immune response, which can have a multifaceted impact on host health. Dysbiosis caused by disturbances in the gut microbiota is associated with susceptibility to many diseases, especially immune-related diseases. Based on the research results in recent years, this paper introduced the mechanism of the interaction between gut microbiota and host immunity, and expounded the role of gut microbiota in the occurrence and development of immune-related diseases, including intestinal system diseases such as inflammatory bowel disease and other systemic diseases such as rheumatoid arthritis, and summarized disease treatment strategies targeting gut microbiota. A better understanding of the research progress of gut microbiota and immune-related diseases will help us in the prevention and management of such diseases, and broaden our path to discover disease intervention targets.

[Microfocal prostate cancer: a clinicopathological analysis of 206 cases].

Objective: To investigate the clinical and pathological features and prognosis of patients with microfocal prostate adenocarcinoma. Methods: Clinical and pathological data of the patients diagnosed with microfocal adenocarcinoma on prostate biopsy at the West China Hospital from 2013 to 2019 were collected. Microfocal adenocarcinoma was defined as follows: Gleason score of 3+3=6, total number of the cores ≥10, number of the positive cores ≤2, and proportion of the tumor in each positive core<50%. Clinicopathological parameters, treatment plans and follow-up data were collected. Pathological information of the biopsy and radical resection specimens was used to analyze the correlation between pathological parameters in the biopsy report and adverse pathological features of radical resection specimens, including increased Gleason score, capsule invasion, positive surgical margin and perineural invasion. Results: A total of 206 cases of microfocal adenocarcinoma were diagnosed on prostate biopsies from 2013 to 2019, accounting for 6.7% of all adenocarcinoma cases. There were 139 cases of 1 positive core and 67 cases of 2 positive cores. Patients with microfocal adenocarcinoma were younger than those with non-microfocal adenocarcinoma (69 years versus 71 years, P<0.001). Compared with patients with non-microfocal adenocarcinoma, the pre-biopsy total prostate specific antigen (tPSA) and free prostate specific antigen (fPSA) levels in patients with microfocal adenocarcinoma were both lower (11.2 µg/L2 versus 23.7 µg/L2; 1.4 µg/L2 versus 3.0 µg/L2, P<0.001), the fPSA/tPSA level was higher (12.9% versus 10.7%, P<0.05), the prostate volume was larger (38.9 mL versus 34.3 mL, P<0.05), and the PSA density was lower (0.3 µg/L2 versus 0.8 µg/L2, P<0.001). 130 patients underwent radical prostatectomy, 30 patients chose active monitoring, 31 patients chose endocrine or radiation therapy, and 15 patients were lost to follow-up. Three patients in the active surveillance group underwent radical prostatectomy for disease progression after 21-39 months observation. Biochemical relapses occurred in two patients in the radical prostatectomy group. The remaining patients have no disease progression or recurrence at present. Compared with radical prostatectomy specimens, Gleason score in the biopsy material was increased in 64/115 patients (55.7%). Among resection excision specimens, 14 cases (12.2%) had extraprostatic extension (EPE), 35 cases (30.4%) had perineural invasion, and 16 cases (13.9%) had a positive margin. Univariate and multivariate analyses showed that low fPSA/tPSA ratio and 2 positive cores were independent risk factors for Gleason score increase in the radical prostatectomy specimens. A low fPSA/tPSA ratio was an independent risk factor for perineural invasion. Low fPSA/tPSA ratio and low prostate volume were associated with a positive margin in radical prostatectomy specimens. Conclusions: In this study, patients diagnosed with microfocal adenocarcinoma on prostate biopsy account for a high proportion of the patients with increased Gleason score in the radical prostatectomy specimens, and there is a certain proportion of adverse pathological features in the radical specimens. Therefore, for the patients with only a small amount of low-grade adenocarcinoma found in biopsy, PSA levels and PSA density should be taken into consideration in treatment selection.

Incidence and risk factors of female urinary incontinence: a 4-year longitudinal study among 24 985 adult women in China.

OBJECTIVE: To estimate the incidence of urinary incontinence (UI), including its subtypes stress UI (SUI), urgency UI (UUI) and mixed UI (MUI), and to examine risk factors for de novo SUI and UUI in Chinese women. DESIGN: Nationwide longitudinal study. SETTING: Six geographic regions of China. PARTICIPANTS: Women aged ≥20 years old were included using a multistage, stratified, cluster sampling method. METHODS: This study was conducted between May 2014 and March 2016, with follow up in 2018. Data on demographics, medical history, lifestyle and physiological and anthropometric information were collected. MAIN OUTCOME MEASUREMENTS: Incidence, rate ratio (RR). RESULTS: Analyses included 24 985 women (mean age 41.9 years).The follow-up response rate was 55.5%, median follow-up time was 3.7 years. The standardised incidences of UI, SUI, UUI and MUI were 21.2, 13.1, 3.0 and 5.1 per 1000 person-years, respectively. Risk factors for de novo SUI included delivery pattern (vaginal spontaneous delivery RR 2.12, 95% CI 1.62-2.78 and instrumental delivery RR 3.30, 95% CI 1.99-5.45), high body mass index (BMI) (overweight RR 1.52, 95% CI 1.33-1.74 and obesity RR 1.67, 95% CI 1.32-2.11), cigarette smoking (RR 1.54, 95% CI 1.12-2.12), chronic cough (RR 1.44, 95% CI 1.17-1.76), diabetes (RR 1.33, 95% CI 1.10-1.60) and older age (50-59 years RR 1.49, 95% CI 1.16-1.90 and 60-69 years RR 1.61, 95% CI 1.22-2.13).The risk factors significantly associated with de novo UUI were age (RR increased from 1.21, 95% CI 0.74-1.99, at 30-39 years to 6.3, 95% CI 3.85-10.30, at >70 years) and diabetes (RR 1.48, 95% CI 1.05-2.09). CONCLUSIONS: The incidence of female UI is 21.2 per 1000 person-years in China. Delivery (vaginal spontaneous delivery, instrumental delivery), high BMI, cigarette smoking, chronic cough, diabetes and older age were risk factors. TWEETABLE ABSTRACT: The incidence of female urinary incontinence was 21.2 per 1000 person-years in China. Delivery, BMI, diabetes and old age are risk factors.

[Risk factors of urinary incontinence in Chinese women based on random forest].

Objective: To explore the risk factors of urinary incontinence (UI) in China by using random forest algorithm, and to evaluate the predictive effect of each risk factor on UI. Methods: A baseline survey with a multistage stratified cluster sampling design was conducted between February 2014 and January 2016, and followed up by telephone from June to December 2018. A total of 55 477 adult women from six provinces of China participated the survey. According to the ratio of 1:1, under sampling method was used to randomly select the same number of women as UI from the non UI women. The data were randomly divided into training set and verification set according to 7:3. The training set was used to establish the random forest model, which including the candidate variables with P<0.2 in univariate analysis, and the verification set was used to verify the predictive effects. Results: A total of 30 658 patients (55.26%, 30 658/55 477) completed the follow-up, the median follow-up time was 3.7 years. Among the 24 985 women without UI at baseline, 1 757 (7.03%, 1 757/24 985) had UI at followed up, including 1 117 (4.47%, 1 117/24 985) with stress UI, 243 (0.97%, 243/24 985) with urgency UI and 397 (1.59%, 397/24 985) with mixed UI. When fixed the number of features as 2 and the number of random trees as 300 in the random forest model, the out of bag error rate estimation was the lowest; with such parameter settings, the classification accuracy was 64.3%, the sensitivity was 64.2%, and the specificity was 64.4%. The top10 predictive UI factors that screening by the variable importance measure in random forest model were obtained as follows: age, parity, delivery pattern, body mass index (BMI), menopause, history of diabetes, education level, history of pelvic surgery, regions, and marital status. Conclusion: We identified the top10 predictive UI factors that screening by the variable importance in random forest model as follows: age, parity, delivery pattern, BMI, menopause, history of diabetes, education level, history of pelvic surgery, regions, and marital status.

[Scientific paradigm of membrane anatomy].

Anatomical plane and fascia have been described in medical behaviors for hundreds of years since the appearance of anatomy and operation. Generally, these descriptions can be sorted into three theories, i.e. plane surgery, fascia theory and mesentery anatomy. However, these theories are difficult to satisfy the scientific paradigm that includes consistency in description, independence in validation, potential to solve practical problems, and the interaction of the above-mentioned theries. Recently, membrane anatomy was proposed as the anatomy of mesentery and its beds in broad sense. Behind it lies fascia membrane/serous membrane structure, as well as inherent life events and general order. Mesentery in broad sense is described as the fascia membrane/serous membrane in serous cavity, which envelops and suspends the organ/tissue and its feeding structures to the posterior wall of the body. Anatomy is the setting/structure, in which life events/functions occur. In the research and discussion of membrane anatomy, abiding by the scientific paradigm and upholding the scientific spirit are the only way to obtain reliable knowledge and the criterion for in-depth scientific research.

[Demonstration and significance on proximal segment of dorsal mesogastrium].

In radical gastrectomy, D2 systemic lymphadenectomy, which includes complete resection of the bursa sac and omentum, and D2 extended lymphadenectomy outside the bursa sac, is a standard procedure accepted by gastrointestinal surgeons generally. However, a series of clinical trials showed that both D2 extended lymphadenectomy and bursectomy could not improve oncologic benefit, but increase surgical risk. These findings showed a lot of conflicts in gastric cancer surgery, gastrointestinal surgery, even in oncological surgery. It was demonstrated that bursa sac and greater omentum were neither mesogastrium nor the proximal segment of dorsal mesogastrium (PSDM), which has been identified recently. Local physiological structures (such as blood vessels and lymphatic nodes) and pathological events (such as lymph nodes metastasis and metastasis V) only occur in mesentery in broad sense (i.e. PSDM). Broken PSDM during radical gastrectomy can result in cancer cell leakage into the operational field. Therefore, complete PSDM excision in the D2 field (D2+CME) is suggested as a better procedure for local advanced gastric cancer, which can get benefits not only in surgical hazard, but also in oncologic result. The results of PSDM research could lead to three changes: (1) resolving some long standing problems in gastric cancer surgery, gastrointestinal surgery, and even oncologic surgery; (2) opening an new era for finding and utilizing extra-intestinal mesentery in broad sense; (3) formulating the theory of membrane anatomy which may update, iterate and upgrade related information of classical anatomy, pathology, surgery and oncology.

Advanced Molecular Characterization Using Digital Spatial Profiling Technology on Immunooncology Targets in Methylated Compared with Unmethylated IDH-Wildtype Glioblastoma.

INTRODUCTION: Glioblastoma (GBM) is the most common primary adult brain tumour with a median overall survival (OS) of 12-15 months. Molecular characterization of multiple immunooncology targets in GBM may help target novel immunotherapeutic strategies. We used NanoString GeoMx® Digital Spatial Profiling (DSP) to assess multiple immunooncology protein targets in methylated versus unmethylated IDH-wild-type glioblastoma. METHODS: NanoString GeoMx® DSP technology uses multiple primary antibodies conjugated to indexing DNA oligos with a UV photocleavable linker. Tissue regions of interest (ROIs) are selected with bound fluorescent antibodies; oligos are released via a UV-mediated linker and quantitated. We used DSP multiplex analysis of 31 immunooncology proteins and controls (CD4, CD14, CD68, CD8A, B7-H3, PD-L1, CD19, FOXP3, CD44, STAT3 (phospho Y705), CD45, Pan Cytokeratin, MS4A1/CD20, CD45RO, PD1, CD3, beta-2 microglobulin, VISTA, Bcl2, GZMB, PTEN, beta-catenin, CD56, Ki-67, STAT3, AKT, p-Akt, S6, Histone H3, IgG Rabbit control, and Mouse IgG control) from ROIs in a cohort of 10 IDH-wild-type glioblastomas (5 methylated and 5 unmethylated). An nCounter platform allowed quantitative comparisons of antibodies between ROIs in MGMT methylated and unmethylated tumours. Mean protein expression counts between methylated and unmethylated GBM were compared using technical and biological replicates. RESULTS: The analysis showed 10/27 immunooncology target proteins were significantly increased in methylated versus unmethylated IDH-wild-type glioblastoma tumour core (false discovery rate (FDR) <0.1 by Benjamini-Hochberg procedure). CONCLUSIONS: NanoString GeoMx® DSP was used to analyse multiple immunooncology protein target expression in methylated versus unmethylated IDH-wild-type glioblastoma. In this small study, there was a statistical increase in CD4, CD14, CD68, CD8A, B7-H3, PDL-1, CD19, FOXP3, CD44, and STAT3 protein expression in methylated versus unmethylated GBM tumour core; however, this requires larger cohort validation. Advanced multiplex immunooncological biomarker analysis may be useful in identifying biomarkers for novel immunotherapeutic agents in GBMs.

Visfatin facilitates gastric cancer malignancy by targeting snai1 via the NF-κB signaling.

BACKGROUND: Visfatin acts as an oncogenic factor in numerous tumors through a variety of cellular processes. Visfatin has been revealed to promote cell migration and invasion in gastric cancer (GC). Snai1 is a well-known regulator of EMT process in cancers. However, the relationship between visfatin and snai1 in GC remains unclear. The current study aimed to explore the role of visfatin in GC. METHODS: The RT-qPCR and western blot analysis were used to measure RNA and protein levels, respectively. The cell migration and invasion were tested by Trans-well assays and western blot analysis. RESULTS: Visfatin showed upregulation in GC cells. Additionally, Visfatin with increasing concentration facilitated epithelial-mesenchymal transition (EMT) process by increasing E-cadherin and reducing N-cadherin and Vimentin protein levels in GC cells. Moreover, endogenous overexpression and knockdown of visfatin promoted and inhibited migratory and invasive abilities of GC cells, respectively. Then, we found that snai1 protein level was positively regulated by visfatin in GC cells. In addition, visfatin activated the NF-κB signaling to modulate snai1 protein expression. Furthermore, the silencing of snai1 counteracted the promotive impact of visfatin on cell migration, invasion and EMT process in GC. CONCLUSION: Visfatin facilitates cell migration, invasion and EMT process by targeting snai1 via the NF-κB signaling, which provides a potential insight for the treatment of GC.