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Ci-Qiu Yang,* Fei Ji,* Hong-Fei Gao, Liu-Lu Zhang, Mei Yang, Teng Zhu, Min-yi Chen, Jie-qing Li, Kun Wang Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kun WangDepartment of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, People’s Republic of ChinaTel/Fax +86 20-83827812-80420Email gzwangkun@126.comBackground: Nipple-sparing mastectomy (NSM) is becoming increasingly accepted as a treatment for breast disease; however, nipple-areolar complex (NAC) necrosis, a frequent severe postoperative complication, inhibits the popularity of this procedure. This study reports the technical aspects and short-term postoperative outcomes of NSM.Methods: A single-center, retrospective review of 110 patients treated with NSM at our institution from November 2015 to September 2018 was performed. The primary outcome was the incidence of NAC necrosis.Results: A total of 130 NSMs performed on 110 patients were included in our study. Median patient age was 42 years. We performed a sharp dissection by using a scalpel, raising 3–5 mm thick flaps, and continuing onto the undersurface of the NAC. None of the 110 patients appeared to have NAC necrosis or mastectomy skin flap necrosis. However, discoloration or ischemia of the NAC with eschar formation presented between postoperative days 3 and 7 in six nipples; four nipples were ischemic, and two were discolored. No infection was detected in any of the 110 patients. All NACs were intact after an average follow-up of 30 months, and no local or systemic recurrence was detected in those breast cancer cases.Conclusion: NSM can be safely performed in properly selected patients. Nipple necrosis was avoided using a special surgical technique, and other complications occurred at an acceptable rate.Keywords: nipple-sparing mastectomy, breast cancer, nipple-areolar complex, sharp dissection

Fei Ji,1,* Wei-Kai Xiao,2,* Ci-Qiu Yang,1,* Mei Yang,1 Liu-Lu Zhang,1 Hong-Fei Gao,1 Yu-Feng Lin,1 Teng Zhu,1 Min-Yi Cheng,1 Wei-Ping Li,1 Wei-Jun Pan,1 Xiao-Sheng Zhuang,1 Kun Wang1 1Department of Breast Cancer, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, P. R. China; 2Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, P.R. China *These authors contributed equally to this work Background: Tumor location in the breast varies, with the highest frequency in the upper outer quadrant and lowest frequency in the lower inner quadrant. Nevertheless, tumors in the central and nipple portion (TCNP) are poorly studied types of breast cancer; therefore, we aimed to clarify the clinicopathological characteristics and prognostic features of TCNP. Methods: Using the Surveillance, Epidemiology, and End Results database, we identifed 105,037 patients diagnosed with tumor in the breast peripheral quadrant (TBPQ) (n=97,046) or TCNP (n=7,991). The chi-squared test was used to compare categorical variables across TCNP and TBPQ. Cox proportional hazard models with hazard ratios were applied to estimate the factors associated with prognosis.Results:The median follow-up was over 43 months. Compared with TBPQ, TCNP patients were signifcantly older (age ≥66 years: 40.4% vs 34.1%, P20 mm size: 46.9% vs 37.3%, P

Hui-Feng Gao,1,2,* Lian-Yu Chen,1,2,* Chien-Shan Cheng,1,2 Hao Chen,1,2 Zhi-Qiang Meng,1,2 Zhen Chen1,21Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 2Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workBackground: Accumulating studies have reported that aberrant expression of SLC5A1 is a negative prognostic factor to various cancer patients.Purpose: Pancreatic cancer tissue has also shown to harbor higher expression of SLC5A1, however how SLC5A1 mediates pancreatic cancer cells growth remains unclear.Methods: In this study, we examined the mRNA and protein expressions of SLC5A1 in human pancreatic tissue and various cell lines. The in vitro and in vivo roles of SLC5A1 in pancreatic cancer were investigated through stably transfected pancreatic cells with shRNA plasmid targeting SLC5A1.Results: Our results observed SLC5A1 was over-expressed in human pancreatic cancer tissues as well as most pancreatic cancer cell lines. Both in vitro and in vivo inhibition of SLC5A1 retarded pancreatic cancer cell growth and progression. The SLC5A1 knockdown mediated growth suppression is mainly regulated by reduced cellular glucose uptake by pancreatic cancer cells. Our further mechanistic observation showed that inhibition of SLC5A1 induced AMPK-dependent mTOR suppression and pharmacological inhibition of AMPK rescued the effect of SLC5A1 blockade. Further protein-protein interaction analysis showed association of SLC5A1 with EGFR and knockdown of EGFR also showed decreased cellular survival and glucose uptake by pancreatic cancer cells.Conclusion: Our findings postulated SLC5A1/EGFR as the potential therapeutic target of pancreatic cancer patients.Keywords: pancreatic cancer, SLC5A1, EGFR, cancer cell survival

Patient-derived organoids (PDOs) may facilitate treatment selection. This retrospective cohort study evaluated the feasibility and clinical benefit of using PDOs to guide personalized treatment in metastatic breast cancer (MBC). Patients diagnosed with MBC were recruited between January 2019 and August 2022. PDOs were established and the efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving organoid-guided treatment (OGT) were matched 1:2 by nearest neighbor propensity scores with patients receiving treatment of physician's choice (TPC). The primary outcome was progression-free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Forty-six PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 78.4% (95% CI 64.9%-91.9%) in predicting clinical responses. Thirty-six OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression-free survival (11.0 months vs. 5.0 months; hazard ratio 0.53 [95% CI 0.33-0.85]; p = .01) and improved disease control (88.9% vs. 63.8%; odd ratio 4.26 [1.44-18.62]) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis in hormone receptor-positive, human epidermal growth factor receptor 2-negative patients demonstrated differentially modulated pathways implicated in DNA repair and transcriptional regulation in those with reduced response to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in those with reduced response to palbociclib. Our study shows that PDO-based functional precision medicine is a feasible and effective strategy for MBC treatment optimization and customization., (© 2024 UICC.)

Wheat (Triticum aestivum L.) is the predominant grain crop and plays a pivotal role in grain production in Xinjiang Uygur Autonomous Region (XUAR), China. Its cultivated area constitutes approximately half of the total sown area of grain crops in XUAR, with 1.14 million hectares in 2021. Fusarium crown rot (FCR) of wheat, caused by Fusarium culmorum (W.G. Smith) Sacc., is one of the most devastating soil-borne diseases known to seriously reduce grain yield (Ma et al. 2024; Saad et al. 2023). In 2016, FCR of wheat, caused by F. culmorum, was firstly identified in Henan Province, China (Li et al. 2016). In June 2023, during the investigation of FCR of wheat in Aksu Prefecture, XUAR, FCR on winter wheat (cv. Xindong 20) was found (82.761349°E, 41.612202°N). The grain-filling period for winter wheat in early June coincided with a period of high temperatures and water demand in Aksu Prefecture. Approximately 8% of the Xindong 20 wheat plants exhibited symptoms of white heads and browning at the stem base, with the disease present in 82% of the wheat fields surveyed. To identify the pathogens, 20 samples of diseased stem basal tissue, each 0.5 cm in length, were collected and sterilized with 75% alcohol for 30s and 5% NaOCl solution for 2 min, followed by three rinses with sterile water. These samples were then plated onto potato dextrose agar (PDA) medium at 25°C for 5 days. A total of 17 isolates with consistent morphological characteristics were obtained using single-spore technique, with an isolation rate of 85%. The isolated strains exhibited rapid growth on PDA, producing fluffy, pale-yellow hyphae, and accumulating a pale-yellow to dark red pigment on the bottom of the medium. On carnation leaf agar (CLA), these strains formed orange colonies due to the aggregation of a large number of macroconidia. The macroconidia were short and thick, with three to four septa and rounded apical cell, averaging 31.94 to 40.96 × 5.62 to 6.71 μm (Magnification of ×400). Microconidia were not observed. These morphological characters were consistent with those of F. culmorum (Leslie and Summerell. 2006). Two isolates (D-9 and D-11) were selected for molecular identification. The EF-1α gene fragment was amplified using primers EF1/EF2 (5'-ATGGGTAAGGARGACAAGAC-3'/5'-GGARGTACCAGTSATCATG-3') as previously described by O'Donnell et al. (1998). The two 665 bp PCR products were sequenced and submitted to GenBank (GenBank Accession No: PP763247 and PP763248) with 99. 7% identity to the published F. culmorum sequences (e.g., OP985478, OP985477, MG195126, KX702638). The molecular identification was further confirmed by F. culmorum species-specific PCR primers FcOIF/FcOIR (Nicholson et al. 1998). The expected PCR products of 553 bp were produced only in F. culmorum. Strains D-9 and D-11 were used to conduct the pathogenicity experiment on 7-day-old winter wheat (cv. Xindong 20) using drip in the lower stem inoculation method with a 10-μl of 106 macroconidia ml-1 suspension, and the control 7-day-old winter wheat were treated with sterile water (Xu et al. 2017). The experiments were replicated five times in a greenhouse at temperatures ranging from 20℃ to 25℃. After 4 weeks, all inoculated wheat seedlings showed stem base browning or even death. No symptoms were observed on the control plants. The fungus was reisolated from all inoculated wheat plants by the method described above and identified by morphological and PCR amplification using F. culmorum species-specific primers FcOIF/FcOIR. No F. culmorum was isolated from the control wheat plants, fulfilling Koch's postulates. To the best of our knowledge, this is the first report of F.culmorum causing FCR on winter wheat in XUAR, China. Considering wheat is the predominant grain crop and plays a pivotal role in grain production in China, necessary measures should be taken to prevent the spread of F. culmorum to other regions.

Purpose: Anthracycline-based or platinum-based neoadjuvant chemotherapy belongs to the standard treatment for early-stage breast cancer (EBC) that is either triple-negative or human epidermal growth factor receptor 2 positive (HER2 +). Currently, there is a paucity of data comparing their impact on health-related quality of life (HRQoL)., Methods: Triple-negative or HER2 + EBC from our two prospective randomized controlled trials, neoCARH and neoCART, were divided into two groups based on the neoadjuvant chemotherapy regimens they received: anthracycline-based or platinum-based group. HRQoL was the exploratory endpoint in these two trials, which was assessed using the European Organization for Research and Treatment of Cancer Quality of Life-Core30 and Breast23 questionnaires. The primary variable of interest was the C30 summary score (C30-SumSc). Assessments were carried out at baseline, after neoadjuvant chemotherapy, and 1 year and 2 years after diagnosis., Results: The mean questionnaires' compliance rate was 95.0%. After neoadjuvant chemotherapy, 210 patients had evaluable HRQoL data, the mean least square change from baseline for the platinum-based group was - 15.997 (95% confidence interval (CI): - 17.877 to - 14.117), and it was - 20.156 (95% CI: - 22.053 to - 18.258) for the anthracycline-based group (difference: 4.159, 95% CI: 1.462 to 6.855, P = 0.003, minimal important difference = 3). For the majority of the domains of interest assessed by the C30 and BR23 questionnaires, the platinum-based group demonstrated superior outcomes in comparison to the anthracycline-based group., Conclusion: Patients receiving platinum-based or anthracycline-based regimens both experienced worsened HRQoL after neoadjuvant chemotherapy; however, the former provided relatively better HRQoL compared with the latter., Clinical Trial Registration: ClinicalTrials.gov: NCT03140553. Registered 4 May 2017 (neoCARH). NCT03154749. Registered 16 May 2017 (neoCART)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fusarium pseudograminearum is an important plant pathogen that invades many crops (Zhang et al. 2018). Since it was first discovered in Australia in 1951, F. pseudograminearum has been reported in many countries and regions and caused huge economic losses (Burgess et al. 2001). In 2012, crown rot of wheat caused by F. pseudograminearum was discovered for the first time in Henan Province, China (Li et al. 2012). Wheat (Triticum aestivum L.) is one of the most important food crops in Xinjiang Uygur Autonomous Region (XUAR), with 1.07 million hectares cultivated in 2020. In June 2023, a survey of crown rot disease was carried out in winter wheat cv. Xindong 20 in Hotan area, XUAR, China (80.148907°E, 37.051474°N). About 5% of wheat plants showed symptoms of crown rot such as browning of the stem base and white head. The disease was observed in 85% of wheat fields. In order to identify the pathogens, 36 pieces of diseased stem basal tissue, 0.5 cm in length, were collected and sterilized with 75% alcohol for 30s and 5% NaOCl solution for 2 min, then rinsed three times with sterile water and placed on potato dextrose agar (PDA) medium at 25°C. A total of 27 isolates with consistent morphological characteristics were obtained using single-spore technique (Leslie and Summerell. 2006), and the isolation rate was 75%. The isolates grew rapidly on PDA, produced large numbers of fluffy white hyphae, and pink pigment accumulated in the medium. The isolates were grown on 2% mung bean flour medium and identified by morphological and molecular methods. Macroconidia were abundant, relatively slender, curved to almost straight, commonly two to seven septate, and averaged 22 to 72 × 1.8 to 4.9 μm. Microconidia were not observed. The morphological characters are consistent with Fusarium (Aoki and O'Donnell. 1999). Two isolates (LP-1 and LP-3) were selected for molecular identification. Primers EF1/EF2 (5'-ATGGGTAAGGARGACAAGAC-3'/5'-GGARGTACCAGTSATCATG-3') were used to amplify a portion of the EF-1α gene (O'Donnell et al. 1998). The two 696 bp PCR products were sequenced and submitted to GenBank. The EF-1α gene sequences (GenBank Accession No: PP062794 and PP062795) shared 99.9% identity (695/696) with published F.pseudograminearum sequences (e.g., OP105187, OP105184, OP105179, OP105173). The identification was further confirmed by F. pseudograminearum species-specific PCR primers Fp1-1/Fp1-2 (Aoki and O'Donnell. 1999). The expected PCR products of 518 bp were produced only in F. pseudograminearum. Pathogenicity tests of LP-1 and LP-3 isolates were performed on 7-day-old seedlings of winter wheat cv. Xindong 20 using the drip inoculation method with a 10-μl of a 106 macroconidia ml-1 suspension near the stem base (Xu et al. 2017). The experiment was repeated five times in a 20 to 25°C greenhouse. Control seedlings were treated with sterile water. After 4 weeks, wheat seedling death and crown browning occurred in the inoculated plants with over 90% incidence. No symptoms were observed in the control plants. The pathogen was reisolated from the inoculated plants by the method described above and identified by morphological and PCR amplification using F. pseudograminearum species-specific primers Fp1-1/Fp1-2. No F. pseudograminearum was isolated from the control plants, fulfilling Koch's postulates. To our knowledge, this is the first report of F. pseudograminearum causing crown rot of winter wheat in XUAR of China. Since F. pseudograminearum can cause great damage to wheat, one of the most important food crops in China, necessary measures should be taken to prevent the spread of F. pseudograminearum to other regions.

An aerobic, haemolytic, Gram-negative and rod-shaped bacterial strain ZY171148 T was isolated from the lung of a dead goat with respiratory disease in Southwest China. The strain grew at 24-39 °C, at pH 6.0-9.0 and in the presence of 0.5-2.0% (w/v) NaCl. Phylogenetic analysis of 16S rRNA gene sequences showed that the strain belongs to the genus Moraxella. The nucleotide sequence similarity analysis of the 16S rRNA gene showed that the strain has the highest similarity of 98.1% to Moraxella (M.) caprae ATCC 700019  T . Phylogenomic analysis of 800 single-copy protein sequences indicated that the strain is a member of the genus Moraxella and forms a separated branch on the Moraxella phylogenetic tree. The strain exhibited the highest orthologous average nucleotide identity (OrthoANI) and average amino acid identity (AAI) values of 77.0 and 77.9% to M. nasibovis CCUG 75921 T and M. ovis CCUG 354 T , respectively. The strain shared the highest digital DNA-DNA hybridization (dDDH) value of 26.2% to M. osloensis CCUG 350 T . The genome G + C content of strain ZY171148 T was 42.6 mol%. The strain had C 18:1 ω9c (41.7%), C 18:0 (11.2%), C 16:0 (14.1%) and C 12:0 3OH (9.7%) as the predominant fatty acids and CoQ-8 as the major respiratory quinone. The strain contained phosphatidylglycerol, phosphatidylethanolamine, cardiolipin, dilysocardiolipin, monolysocardiolipin and phosphatidic acid as the major polar lipids. β-haemolysis was observed on Columbia blood agar. All results confirmed that strain ZY171148 T represents a novel species of the genus Moraxella, for which the name Moraxella haemolytica sp. nov. is proposed, with strain ZY171148 T  = CCTCC AB 2021471 T  = CCUG 75920 T as the type strain., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To compare the surgical safety and postoperative quality of life between proximal gastrectomy with double tract reconstruction (PG-DT) and proximal gastrectomy with gastric tube reconstruction (PG-GT) for proximal gastric cancer. Methods: This was a retrospective cohort study of clinical and follow-up data of 99 patients with proximal gastric cancer who had undergone double tract or gastric tube surgery in Nanjing Drum Tower Hospital from January 2016 to September 2021. We allocated them to two groups according to surgical procedure, namely a double tract group (PG-DT, 50 patients) and gastric tube group (PG-GT, 49 patients). Proximal gastrectomy with double tract reconstruction entails constructing a Roux-en-Y esophagojejunostomy after severing the proximal stomach, and then constructing a side-to-side anastomosis between the residual stomach and the jejunum to establish an anti-reflux barrier and thus minimize postoperative gastroesophageal reflux. Proximal gastrectomy with gastric tube reconstruction entails severing the proximal gastric stomach, constructing a tubular shaped gastric remnant, and then using a linear stapler to directly anastomose the posterior wall of the esophagus to the anterior wall of the resultant gastric tube. The primary end point was the quality of life of the two groups 1 year postoperatively (post-gastrectomy syndrome assessment scale: the higher the scores for change in body mass, food intake per meal, meal quality subscale, total physical health measurement, and total mental health measurement, the better the quality-of-life, and the higher the scores for other indicators, the worse the quality-of-life). The secondary end points were intraoperative and postoperative status, changes in nutritional status 1, 3, 6, and 12 months postoperatively, and long-term postoperative complications (gastroesophageal reflux, anastomotic stenosis, intestinal obstruction, and gastric emptying disorder 1 year postoperatively). Results: In the PG-DT group, there were 35 (70%) men and 15 (30%) women, 33 (66.0%) patients were aged <65 years, and 37 (74.0%) of them had a body mass index of 18-25 kg/m 2 ; whereas in the PG-GT group, there were 41 (83.7%) men and eight (16.3%) women, 21 (42.9%) patients aged <65 years, and 34 (69.4%) patients with a body mass index of 18-25 kg/m 2 . There were no significant differences in baseline data between the two groups except for age ( P =0.021). There were no significant differences in intraoperative blood loss, number of lymph node dissected, length of hospital stay, and incidence of perioperative complications between the two groups (all P >0.05). Compared with the PG-GT group, the incidence and severity of postoperative reflux esophagitis were significantly lower in the PG-DT group (4.0% [2/50] vs. 26.5% [13/49], χ 2 =13.507, P =0.009). The incidences of postoperative anastomotic stenosis, intestinal obstruction, and gastric retention did not differ significantly between the two groups (all P >0.05). Patients in the PG-DT group had better quality-of-life scores for esophageal reflux (2.8 [2.3,4.0] vs. 4.8 [3.8,5.0], Z =3.489, P <0.001), eating discomfort (2.7 [1.7,3.0] vs. 3.3 [2.7,4.0 ], Z =3.393, P =0.001), and total symptoms (2.3 [1.7,2.7] vs. 2.5 [2.2,2.9], Z =2.243, P =0.025) than those in the gastric tube group; The scores for postoperative symptoms (2.0 [1.0,3.0] vs. 2.0 [2.0, 3.0], Z =2.127, P =0.033), meals consumed (2.0 [1.0, 2.0] vs. 2.0 [2.0, 3.0], Z =3.976, P <0.001), work (1.0 [1.0, 2.0] vs. 2.0 [1.0, 2.0], Z =2.279, P =0.023] and daily life (1.7 [1.3, 2.0] vs. 2.0 [2.0, 2.3], Z =3.950, P <0.001) were better in the PG-DT than the PG-GT group. Patients in the PG-GT group scored better than those in the PG-DT group for somatic symptoms, such as anal evacuation (3.0 [2.0, 4.0] vs. 3.5 [2.0, 5.0], Z =2.345, P =0.019). There were no significant differences in hemoglobin, serum albumin, serum total protein, or weight loss 1 year postoperatively between the two groups (all P >0.05). Conclusions: The safety of double tract anastomosis for proximal gastric cancer is comparable to that of gastric tube surgery. Compared with gastric tube surgery, double tract anastomosis achieves less esophageal reflux and better quality of life, making it a preferable surgical procedure for proximal gastric cancer.

Background: Pancreatic cancer (PC) is a highly lethal malignancy that requires effective novel therapies. M2 macrophages are abundant in the PC microenvironment and promote cancer progression. Exosomes are emerging mediators of the crosstalk between cancer cells and the microenvironment. This study was conducted to explore the role of M2 macrophage-derived exosomes in PC., Methods: Exosomes derived from M2 macrophages were extracted. miR-193b-3p and TRIM62 were overexpressed or silenced to examine their function in PC. Luminescence assays were used to investigate the interaction between miR-193b-3p and TRIM62. Cell proliferation was examined by EdU staining. Would healing and transwell assays were applied to evaluate cell migration and invasion. Co-immunoprecipitation was used to assess the interaction between TRIM62 and c-Myc. Gene and protein expressions were analyzed by quantitative RT-PCR and immunoblotting, respectively., Results: M2 macrophage-derived exosomal miR-193b-3p promoted the proliferation, migration, invasion, and glutamine uptake of SW1990 cells. Mechanism study revealed that TRIM62 is a target of miR-193b-3p. TRIM62 inhibited the proliferation, migration, invasion, and glutamine uptake of SW1990 cells by promoting c-Myc ubiquitination. Our data also suggested that TRIM62 expression negatively correlated with miR-193b-3p and c-Myc expression. High-expression of miR-193b-3p and c-Myc predicts poor prognosis, whereas low-expression of TRIM62 predicts poor prognosis in patients with PC., Conclusion: M2 macrophage-derived exosomal miR-193b-3p enhances the proliferation, migration, invasion, and glutamine uptake of PC cells by targeting TRIM62, resulting in the decrease of c-Myc ubiquitination. This study not only reveals the mechanism underlying the crosstalk between M2 macrophages and PC cells but also suggests a promising therapeutic target for PC., (© 2023. The Author(s).)

Background: Evidence for the preferred neoadjuvant therapy regimen in triple-negative breast cancer (TNBC) is not yet established., Methods: Literature search was conducted from inception to February 12, 2022. Phase 2 and 3 randomized controlled trials (RCTs) investigating neoadjuvant therapy for TNBC were eligible. The primary outcome was pathologic complete response (pCR); the secondary outcomes were all-cause treatment discontinuation, disease-free survival or event-free survival (DFS/EFS), and overall survival. Odd ratios (OR) with 95% credible intervals (CrI) were used to estimate binary outcomes; hazard ratios (HR) with 95% CrI were used to estimate time-to-event outcomes. Bayesian network meta-analysis was implemented for each endpoint. Sensitivity analysis and network meta-regression were done., Results: 41 RCTs (N = 7109 TNBC patients) were eligible. Compared with anthracycline- and taxane-based chemotherapy (ChT), PD-1 inhibitor plus platinum plus anthracycline- and taxane-based ChT was associated with a significant increased pCR rate (OR 3.95; 95% CrI 1.81-9.44) and a higher risk of premature treatment discontinuation (3.25; 1.26-8.29). Compared with dose-dense anthracycline- and taxane-based ChT, the combined treatment was not associated with significantly improved pCR (OR 2.57; 95% CrI 0.69-9.92). In terms of time-to-event outcomes, PD-1 inhibitor plus platinum plus anthracycline- and taxane-based ChT was associated with significantly improved DFS/EFS (HR 0.42; 95% CrI 0.19-0.81)., Conclusions: PD-1 inhibitor plus platinum and anthracycline- and taxane-based ChT was currently the most efficacious regimen for pCR and DFS/EFS improvement in TNBC. The choice of chemotherapy backbone, optimization of patient selection with close follow-up and proactive symptomatic managements are essential to the antitumor activity of PD-1 inhibitor., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the safety and clinical efficacy of bilateral percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral burst fractures. Methods: It was a prospective study, 28 patients with osteoporotic thoraco-lumbar burst fractures who were treated in Beijing Chao-Yang Hospital from January 2021 to July 2021 were included, including 10 males and 18 females, with a median age of 73.6 years (range: 56.0-87.0 years). The X-ray radiographs, bone mineral density (BMD), CT three-dimensional reconstruction scan and MRI were taken and measured before operation to observe the fracture location and the posterior wall of the vertebral body, and further to determine the diagnosis. The X-ray radiographs and CT three-dimensional reconstruction scans were taken on the first day after operation and the last follow-up to observe whether there were bone cement leakage or not. The changes of kyphosis angle (KA), the height of anterior wall (HAW) and the height of posterior wall (HPW) before the operation, on the 1st day post operation and at the last follow-up were recorded. The visual analogue scale (VAS) of back pain and Oswestry dysfunction index (ODI) before the operation, 1 day post operation and at the last follow-up were used to evaluate the clinical effect of the operation. Results: All the patients were followed up for (12.2±6.0) months. The HAW on the 1st day post operation [(22.5±2.0) mm] was significantly increased as compared with that before the operation [(21.2±2.4) mm] ( P <0.05). The HAW at the last follow-up [(18.9±1.6) mm] decreased signficantly as compared with that on the 1st day post opertion [(22.5±2.0) mm] ( P <0.05). The HPW was also significantly corrected after surgery ( P <0.05). At the end of the follow-up, the HPW [(27.2±1.3) mm] was comparable with that on the 1st day after surgery [(27.5±1.6) mm] ( P >0.05). The KA on the 1st day after the operation (14.2°±1.5°) decreased significantly when compared with that before the operation (18.8°±1.3°) ( P <0.05), but it was increased to 17.6°±1.4° at the last follow-up and was higher than that on the 1st day after the operation ( P <0.05). There were bone cement leakage in 5 cases and adjacent vertebral fracture in 1 case. The VAS and ODI scores were all significantly lower on the 1st day and at last follow-up than that before the operation (all P <0.05). Conclusions: Bilateral PKP is effective, safe and reliable in the treatment of osteoporotic vertebral burst fracture. Careful evaluation of preoperative imaging data, accurate puncture and timing of bone cement injection are the key factors to ensure the success of the operation.

The lack of reliable drugs is a therapeutic challenge of advanced breast cancers (ABCs). Resveratrol (Res) exerts inhibitory effects on breast cancer cell lines and animal models, while its efficacy against individual breast cancer cases remains unknown. This study aims to use ABC-derived organoids (ABCOs) as the ex vivo therapeutic platform to clarify the effectiveness of resveratrol against different ABC subtypes. Immunohistochemical staining confirmed that the ABCOs maintained their original tumors' ER, PR, HER2, and Ki67 expression patterns. ABCO proliferation and viability tests showed >50% cell death rates in 79.2% (19/24) of Res-treated, 28.6% (2/7) fulvestrant-treated, 66.7% (4/6) paclitaxel-treated, and 66.7% (6/9) gemcitabine-treated ABCOs. pSTAT3 nuclear translocation was more frequent in Res-sensitive (17/19; 89.47%) than that (1/5; 20%) of Res-insensitive ABCOs, which were suppressed upon Res treatment. Statistical analysis revealed a close correlation of STAT3 activation with the efficacy of Res, but not related to tumor receptor expression patterns (ER, PR, HER2) and pathological classification. We demonstrate for the first time the higher efficacy and broader spectrum of Res against different subtypes of ABCOs in comparison with that of conventional antibreast cancer drugs, providing an alternative approach for better management of ABCs., (© 2022 John Wiley & Sons Ltd.)

Background: For patients with breast cancer who receive docetaxel chemotherapy, taxane-associated acute pain syndrome (T-APS), considered a form of neural pathology, is a significant clinical problem. We evaluated the effect of prophylactic etoricoxib on T-APS in patients with breast cancer., Materials and Methods: We conducted a phase II randomised trial including 144 patients with breast cancer receiving four cycles of docetaxel-based chemotherapy. Patients were randomised in the ratio 1:1 to receive prophylactic etoricoxib (60 mg, Day 1 to Day 8) or no prophylactic treatment. The primary end-point was the overall incidence of T-APS across all cycles. Secondary end-points included the incidence of severe pain (greater than 5 on a scale 0-10); severity and duration of T-APS; Functional Assessment of Cancer Therapy-Breast subscale; chronic sensory and motor neurotoxicity and adverse events., Results: The overall incidence of T-APS across all cycles of chemotherapy in the etoricoxib group was 57.1%, while that in the control group was 91.5% (P < 0.001). The incidences of severe T-APS were 11.4% and 54.9% for the etoricoxib and control groups, respectively (P < 0.001). The mean Functional Assessment of Cancer Therapy-Breast subscale score of the etoricoxib group (103.79-107.24) was significantly higher than that of the control group (93.88-96.71) (P = 0.001 at cycle 1 and P < 0.001 at cycles 2-4). After four cycles of docetaxel chemotherapy, the etoricoxib group demonstrated a significantly higher mean Functional Assessment of Cancer Treatment Neurotoxicity subscale score than the control group (38.46, 95% CI: 37.63-39.29; 34.59, 95% CI: 33.73-35.45, respectively; P < 0.001). Electromyography showed that most peripheral sensory nerves in the etoricoxib group had significantly improved action potential amplitudes and conduction velocities compared with those in the control group., Conclusion: Prophylactic use of etoricoxib could significantly reduce the incidence and severity of docetaxel-induced acute pain syndrome and potentially decrease docetaxel-induced peripheral neuropathy., Trial Registration: ClinicalTrials.gov, NCT04565600., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Pseudostellaria heterophylla is authentic traditional Chinese herbal medicine in Fujian Province. P. hete-rophylla suffers from serious consecutive monoculture problems. Fallow can alleviate such problems, but the mecha-nism is still unclear. In this study, high-throughput sequencing was performed to analyze the changes in soil microbial community structure and diversity in the P. heterophylla soil at different fallow ages as well as their relationships with soil physicochemical properties and phenolic acids. The results showed that fungal community diversity decreased but bacterial community diversity increased in fallow soils compared with the control soil of P. heterophy-lla . For bacterial communities, the relative abundance of Acidobacteria increased, while that of Proteobacteria and Actinobacteria decreased in fallow soils. For fungal communities, the relative abundance of dominant phyla had no significant difference between fallow and control soils. Soil acidity and organic matter content showed a trend of weakening and decreasing, respectively, with the increases of fallow years. In addition, with the increases of fallow years, the content of phenolic acids in soil, including benzoic acid and salicylic acid, showed significant decrease, while some other phenolic acids such as p-coumaric acid were accumulated obviously. Taken together, fallow could efficiently ameliorate the structure of soil microbial community and soil properties of P. heterophylla , and thus alleviate the effects of continuous cropping.

The dataset presents the raw data collected through an online survey of senior high school students and their parents from 24 provinces, municipalities and autonomous regions (96 cities) of China. We conducted the online survey using electronic self-administered questionnaires designed as student-version and parent-version during 26th February and 4th March of 2020. The questionnaires were designed using the online survey tool Sojump (Shanghai Information Co.), and released through WeChat platform (Tencent Corp) following principals-head teachers-students/parents approach. All the students and the parents were asked to answer the questions voluntarily and anonymously after reading informed consent at the fore page of the questionnaires. The information collected from students included: 1) demographic characteristics, including sex, date of birth, name of high school, academic year, and self-evaluated performance level; 2) educational levels and occupations of parents; 3) degree preferences, including the willingness to learn medicine (prior and post COVID-19 outbreak), preferred medical career (clinician, public health practitioner, pharmacist, nurse or others), and main motivations for selecting or unselecting medical study; 4) infection of COVID-19 in acquaintances; 5) health literacy level on infectious diseases assessed using the Infectious Disease-specific Health Literacy Scale (IDSHL), and 6) anxiety level evaluated using the Chinese version of the Generalized Anxiety Disorder Screener (GAD-7). Information collected from parents included sex of their children and name of high school attended by their children, as well as their own educational level, occupation, anxiety symptoms, attitude toward their children's studying medicine, and main reasons for supportive or unsupportive attitudes, which were similar to the main motivations or de-motivations for medical study listed in the student-version questionnaire. Date and time for completion of the questionnaire were auto-recorded by the Sojump system. The dataset was established at the early stage of pandemic of COVID-19, and is valuable for understanding the instant psychological impacts of the outbreak of an emerging fatal infectious disease on senior high school students and their patents, and can provide evidence for policymakers on mental health intervention and medical education in China. The data are provided with this article., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s). Published by Elsevier Inc.)

Background: The outbreak of COVID-19 has been a big challenge for senior high school students in China who are facing tremendous pressure of the highly competitive College Entrance Examination., Methods: To evaluate the psychological impact of the event in the population, we conducted an anonymous online survey among senior high school students in China between 26 Feb and 4 March, 2020. Information collected included demographic characteristics, attitude toward medical study, infection of COVID-19 in acquaintances, anxiety symptoms evaluated using the GAD-7, and health literacy level measured using the IDSHL., Results: Of 21,085 participants, 3,575 (17.0%), 943 (4.5%) and 448 (2.1%) reported with mild, moderate, and severe anxiety. Female, higher academic year, worse self-evaluated academic performance, negative attitude toward medical study, living in Hubei province and having acquaintance infected with COVID-19 were significantly associated with anxiety level, while higher education level of mother and higher IDSHL score were associated with a lower risk. The score of IDSHL, particularly of the domain "infectious disease prevention", was associated with the GAD-7 score in a linear pattern (β=-0.0371, p<0.01)., Limitations: Limitations included the cross-sectional study design unable to infer the casual relationship, anonymous survey, selection bias and self-reported anxiety disorder levels., Conclusions: The results suggested that COVID-19 outbreak may increase anxiety level in senior high school students in China. The anxiety related factors observed in this study may help to identify vulnerable individuals and develop interventions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Akabane virus (AKAV) has been detected in a variety of host species in China, but there are only limited records of its occurrence in goats. However, more attention needs to be paid to understanding the diversity of viruses in this species. The aim of the study was to explore the genotype characteristics and variation trend of AKAV and their relationship with virulence in Yunnan, China., Material and Methods: Blood samples were collected from goats during routine surveillance of goat diseases in Yunnan province in 2019. The AKAV CX-01 strain was isolated using BHK-21 cells. To understand pathogenicity, the virus was intraperitoneally (IP) and intracerebrally (IC) inoculated into suckling mice and tissue samples were subsequently analysed histopathologically and immunohistochemically., Results: Akabane virus CX-01 strain induced encephalitis and impairment of the central nervous system with fatal consequences. Phylogenetic analysis based on the ORF sequences of the small segments indicated that the AKAV isolate used was most closely related to the GD18134/2018 Chinese midge and bovine NM BS/1strains, while phylogenetic analysis based on the medium segments showed a close relationship between CX-01 and the Chinese GLXCH01 strain., Conclusion: The CX-01 isolate was related to AKAV genogroup Ia and probably originated from a recombination of different strains., Competing Interests: Conflict of Interest Conflict of Interests Statement: The authors declare that there is no conflict of interests regarding the publication of this article., (© 2022 H.F. Gao et al., published by Sciendo.)

Previous studies have shown that the addition of carboplatin to neoadjuvant chemotherapy improved the pathologic complete response (pCR) rate in patients suffering from triple-negative breast cancer (TNBC) and patients who obtained a pCR could achieve prolonged event-free survival (EFS) and overall survival (OS). However, no studies have assessed the effects of the combination of docetaxel and carboplatin without anthracycline with taxane-based and anthracycline-based regimens. The NeoCART study was designed as a multicenter, randomized controlled, open-label, phase II trial to assess the efficacy and safety of docetaxel combined with carboplatin in untreated stage II-III TNBC. All eligible patients were randomly assigned, at a 1:1 ratio, to an experimental docetaxel plus carboplatin (DCb) for six cycles group (DCb group) or an epirubicin plus cyclophosphamide for four cycles followed by docetaxel for four cycles group (EC-D group). PCR (ypT0/is ypN0) was evaluated as the primary outcome. Between 1 September 2016 and 31 December 2019, 93 patients were randomly assigned and 88 patients were evaluated for the primary endpoint (44 patients in each group). In the primary endpoint analysis, 27 patients in the DCb group (61.4%, 95% CI 47.0-75.8) and 17 patients in the EC-D group achieved a pCR (38.6%, 95% CI 24.3-53.0; odds ratio 2.52, 95% CI 2.4-43.1; P noninferiority = .004). Noninferiority was met, and the DCb regimen was confirmed to be superior to the EC-D regimen (P = .044, superiority margin of 5%). At the end of the 37-month median follow-up period, OS and EFS rates were equivalent in both groups., (© 2021 UICC.)

Helical structures continue to inspire, prompted by examples such as DNA double-helix and alpha-helix in proteins. Most synthetic polymers also crystallize as helices, which relieves steric clashes by twisting, while keeping the molecules straight for their ordered packing. In columnar liquid crystals, which often display useful optoelectronic properties, overall helical chirality can be induced by inclusion of chiral chemical groups or dopants; these bias molecular twist to either left or right, analogous to a magnetic field aligning the spins in a paramagnet. In this work, however, we show that liquid-crystalline columns with long-range helical order can form by spontaneous self-assembly of straight- or bent-rod molecules without inclusion of any chiral moiety. A complex lattice with Fddd symmetry and 8 columns per unit cell (4 right-, 4 left-handed) characterizes this "antiferrochiral" structure. In selected compounds it allows close packing of their fluorescent groups reducing their bandgap and giving them promising light-emitting properties., (© 2022. The Author(s).)

Background: Pancreatic cancer (PC) is a highly lethal disease and an increasing cause of cancer-associated mortality worldwide. Interferon regulatory factors (IRFs) play vital roles in immune response and tumor cellular biological processes. However, the specific functions of IRFs in PC and tumor immune response are far from systematically clarified. This study aimed to explorer the expression profile, prognostic significance, and biological function of IRFs in PC., Results: We observed that the levels of IRF2, 6, 7, 8, and 9 were elevated in tumor compared to normal tissues in PC. IRF7 expression was significantly associated with patients' pathology stage in PC. PC patients with high IRF2, low IRF3, and high IRF6 levels had significantly poorer overall survival. High mRNA expression, amplification and, deep deletion were the three most common types of genetic alterations of IRFs in PC. Low expression of IRF2, 4, 5, and 8 was resistant to most of the drugs or small molecules from Genomics of Drug Sensitivity in Cancer. Moreover, IRFs were positively correlated with the abundance of tumor infiltrating immune cells in PC, including B cells, CD8+ T cells, CD4+ T cells, macrophages, Neutrophil, and Dendritic cells. Functional analysis indicated that IRFs were involved in T cell receptor signaling pathway, immune response, and Toll-like receptor signaling pathway., Conclusions: Our results indicated that certain IRFs could serve as potential therapeutic targets and prognostic biomarkers for PC patients. Further basic and clinical studies are needed to validate our findings and generalize the clinical application of IRFs in PC., (© 2022. The Author(s).)

Immune response which involves distinct immune cells is associated with prognosis of breast cancer. Nonetheless, less study have determined the associations of different types of immune cells with patient survival and treatment response. In this study, A total of 1,502 estrogen receptor(ER)-negative breast cancers from public databases were used to infer the proportions of 22 subsets of immune cells. Another 320 ER-negative breast cancer patients from Guangdong Provincial People's Hospital were also included and divided into the testing and validation cohorts. CD8 + T cells, CD4 + T cells, B cells, and M1 macrophages were associated with favourable outcome (all p <0.01), whereas Treg cells were strongly associated with poor outcome ( p = 0.005). Using the LASSO model, we classified patients into the stromal immunotype A and B subgroups according to immunoscores. The 10 years OS and DFS rates were significantly higher in the immunotype A subgroup than immunotype B subgroup. Stromal immunotype was identified as an independent prognostic indicator in multivariate analysis in all cohorts and was also related to pathological complete response(pCR) after neoadjuvant chemotherapy. The nomogram that integrated the immunotype and clinicopathologic features showed good predictive accuracy for pCR and discriminatory power. The stromal immunotype A subgroup had higher expression levels of immune checkpoint molecules (PD-L1, PD-1, and CTLA-4) and cytokines (IL-2, INF-γ, and TGF-β). In addition, patients with immunotype A and B diseases had distinct mutation signatures. Therefore, The stromal immunotypes could predict survival and responses of ER-negative breast cancer patients to neoadjuvant chemotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ji, Yuan, Gao, Xu, Yang, Yang, Zhang, Yang, Li, Zhu, Cheng, Wu and Wang.)

Background: The benefit of adjuvant cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors with endocrine therapy (ET) in hormone receptor-positive, human epidermal growth factor 2 receptor-negative (HR+/HER2-) early breast cancer (EBC) is uncertain. Hence, we performed a meta-analysis to determine the efficacy and safety of adjuvant CDK4/6 inhibitors plus ET and to identify potential preferred subpopulations for this regimen., Methods: A literature search was conducted in PubMed, Embase, Cochrane databases up to Jan 15, 2021. Hazard ratios (HRs) for invasive disease-free survival (IDFS) and risk ratios (RRs) for grade 3/4 adverse events (AEs) and treatment discontinuation were extracted. Analysis with predefined subgroup variables was done. Trial sequential analysis (TSA) was performed to assess the conclusiveness of survival outcomes., Results: Three trials were eligible (N = 12647). Compared with ET, adjuvant CDK4/6 inhibitors with ET prolonged IDFS in patients with HR+/HER2- EBC (HR 0.87, 95% CI 0.76-0.98, p = 0.03, I 2  = 19%), with positive therapeutic responses observed in patients with N2/N3 nodal status (HR 0.83, 95% CI 0.71-0.97, p = 0.02, I 2  = 0%). None of the cumulative z-curves crossed the trial monitoring boundaries in TSA, and no reliable conclusion could be drawn. The combination treatment carried a higher risk of grade 3/4 AEs (RR 4.14, 95% CI 3.33-5.15, p < 0.00001) and an increase in treatment discontinuation due to AEs (RR 19.16, 95% CI 9.27-39.61, p < 0.00001)., Conclusions: Adjuvant CDK4/6 inhibitors with ET might provide survival benefit in HR+/HER2- EBC. A statistically significantly improved IDFS was only observed in N2/N3 subgroup. However, overall evidence favoring the use of this combination regimen was inadequate., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Activation of inflammasomes has been reported in human pancreatic adenocarcinoma (PAAD); however, the expression pattern and functional role of inflammasome-related proteins in PAAD have yet to be identified. In this study, we systemically examined the expression and role of different inflammasome proteins by retrieving human expression data. Several genes were found to be differentially expressed; however, only interferon-inducible protein 16 (IFI16) expression was found to be adversely correlated with the overall survival of PAAD patients. Overexpression of IFI16 significantly promoted tumor growth, increased tumor size and weight in the experimental PAAD model of mice, and specifically increased the population of tumor-associated macrophages (TAMs) in the tumor microenvironment. Depletion of TAMs by injection of liposome clodronate attenuated the IFI16 overexpression-induced tumor growth in PAAD. In vitro treatment of conditioned medium from IFI16-overexpressing PAAD cells induced maturation, proliferation, and migration of bone marrow-derived monocytes, suggesting that IFI16 overexpression resulted in cytokine secretion that favored the TAM population. Further analysis suggested that IFI16 overexpression activated inflammasomes, thereby increasing the release of IL-1β. Neutralization of IL-1β attenuated TAM maturation, proliferation, and migration induced by the conditioned medium from IFI16-overexpressing PAAD cells. Additionally, knockdown of IFI16 could significantly potentiate gemcitabine treatment in PAAD, which may be associated with the reduced infiltration of TAMs in the tumor microenvironment. The findings of our study shed light on the role of IFI16 as a potential therapeutic target for PAAD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Cheng, Gao, Chen, Lv, Xu, Shen, Xie and Zheng.)

Background: Although dual blockade HER2-based neoadjuvant chemotherapy is associated with excellent outcomes for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, pertuzumab is not available to all patients due to cost. The optimal neoadjuvant chemotherapy for HER2-positive breast cancer in the presence of a single HER2 blockade is unknown. This study aimed to compare the efficacy and safety of epirubicin/cyclophosphamide followed by docetaxel/trastuzumab (EC-TH) with docetaxel/carboplatin/trastuzumab (TCH) neoadjuvant setting for HER2-positive breast cancer under the single HER2 blockade., Methods: Patients with stage II-IIIC HER2-positive breast cancer were randomly assigned to either eight cycles of EC-TH every 3 weeks during all chemotherapy cycles, or six cycles of TCH every 3 weeks. The primary endpoint was pathological complete response (pCR) (defined as the absence of invasive tumor cells in breast and axilla, ypT0/is ypN0)., Results: From May 2017 to November 2019, 140 patients were randomly assigned, and 135 patients were ultimately found evaluable for the primary endpoint. The pCR was recorded in 25 of 67 patients [37.3%; 95% confidence interval (CI), 25.8-50.0] in the EC-TH group and in 38 of 68 patients (55.9%, 95% CI, 43.3-67.9) in the TCH group ( p  = 0.032). The most common adverse events (AEs) were neutropenia in 24 of 67 (35.8%) patients in the EC-TH group versus 27 of 68 (39.7%) in the TCH group ( p  = 0.642), anemia in 33 of 67 (49.3%) patients in the EC-TH group versus 34 of 68 (50.0%) in the TCH group ( p  = 0.931), and thrombocytopenia in five of 67 (7.5%) patients in the EC-TH group versus 17 of 68 (25.0%) in the TCH group ( p  = 0.006)., Conclusion: For patients receiving the single HER2 blockade trastuzumab for HER2-positive breast cancer, TCH regimen might be a preferred neoadjuvant therapy., Trial Registration: This trial was registered with ClinicalTrials.gov identifier: NCT03140553) on 2 May 2017., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

Morbidity and mortality caused by infectious diseases rank first among all human illnesses. Many pathogenic mechanisms remain unclear, while misuse of antibiotics has led to the emergence of drug-resistant strains. Infectious diseases spread rapidly and pathogens mutate quickly, posing new threats to human health. However, with the increasing use of high-throughput screening of pathogen genomes, research based on big data mining and visualization analysis has gradually become a hot topic for studies of infectious disease prevention and control. In this paper, the framework was performed on four infectious pathogens (Fusobacterium, Streptococcus, Neisseria, and Streptococcus salivarius) through five functions: 1) genome annotation, 2) phylogeny analysis based on core genome, 3) analysis of structure differences between genomes, 4) prediction of virulence genes/factors with their pathogenic mechanisms, and 5) prediction of resistance genes/factors with their signaling pathways. The experiments were carried out from three angles: phylogeny (macro perspective), structure differences of genomes (micro perspective), and virulence and drug-resistance characteristics (prediction perspective). Therefore, the framework can not only provide evidence to support the rapid identification of new or unknown pathogens and thus plays a role in the prevention and control of infectious diseases, but also help to recommend the most appropriate strains for clinical and scientific research. This paper presented a new genome information visualization analysis process framework based on big data mining technology with the accommodation of the depth and breadth of pathogens in molecular level research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Sun, Hou, Du, Wang, Du, Yu, Cai, Yu, Li, Luo, Shen, Lu, Li, Zhang, Gao, Ma, Lin and Cao.)

Purpose: The aim of this study was to explore the value of adjuvant chemotherapy in patients with early-stage ER/PR-positive mucinous carcinoma., Methods: We identified early-stage ER/PR-positive mucinous carcinoma patients in the Surveillance, Epidemiology, and End Results (SEER) database. We used propensity-score matching (PSM) analysis to eliminate selection bias and differences in baseline characteristics. Univariate and multivariate analyses were performed to identify significant prognostic factors. The primary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS), which were evaluated with the Kaplan-Meier method., Results: After propensity score matching, 805 pairs were selected. Patients with early-stage ER/PR-positive mucinous adenocarcinoma in the chemotherapy group had a better OS, but not BCSS, than those in the nonchemotherapy group after PSM (OS: p < 0.001; BCSS: p = 0.285). After stratifying by tumor size and lymph node status, adjuvant chemotherapy could significantly improve the OS of early-stage ER/PR-positive patients with tumors larger than 3 cm (p = 0.004) if they had negative lymph nodes (LNs). For patients positive LNs, the OS was significantly different between the chemotherapy group and the non-chemotherapy group when the tumors were larger than 1 cm (T = 1-2.9 cm, p = 0.006; T＞3 cm, p = 0.049, respectively)., Conclusion: Adjuvant chemotherapy maybe improves prognosis in patients with negative LNs and tumors larger than 3 cm, or patients with LNs metastasis and tumors larger than 1 cm. We suggest considering clinical characteristics meanwhile when deciding chemotherapy or not. Randomized controlled trials (RCT) are expected to confirm our results in the future., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest in this work., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study aimed to compare the efficacy and safety of the EC-T (4 cycles of epirubicin 90 mg/m2 + cyclophosphamide 600 mg/m2, followed by 4 cycles of docetaxel 75 mg/m2) and TCb (6 cycles of docetaxel 75 mg/m2, intravenous drip (ID), day 1 + carboplatin AUC 6, ID, day 1) neoadjuvant regimens in patients with TOP2A-normal stage II-III breast cancer. This study analyzed 280 patients enrolled from three studies registered with ClinicalTrials.gov (NCT03140553, NCT03154749, NCT03507465) with early TOP2A-normal stage II-III breast cancer who received neoadjuvant chemotherapy, including 100 patients who received the EC-T regimen and 180 patients who received the TCb regimen. The primary endpoint was the ratio of RCB 0/1 (residual cancer burden 0/1) after neoadjuvant chemotherapy. The secondary endpoint was the safety of the two groups. There was no significant difference in the ratio of RCB 0/1 between the two groups (23% vs. 23.9%, p=0.614). Among the triple-negative breast cancer patients, the efficacy did not differ between the two groups (40% vs. 32%, p=0.52). Among the lymph node metastasis patients, the efficacy of the EC-T group was significantly better than that of the TCb group (14% vs. 2.6%, p=0.03). Regarding the side effects, the incidence of grade 3/4 anemia was higher in the EC-T group than in the TCb group (21.0% vs. 8.33%, p=0.002), while the incidence of grade 3/4 neutropenia was higher in the EC-T group than in the TCb group (17% vs. 14.44%, p=0.570), and the incidence of grade 3/4 thrombocytopenia was low in each group (EC-T group: 6 % and TCb group: 7.22%, p=0.697). In the EC-T group, grade 3/4 nausea and vomiting occurred in 5 patients. The EC-T group showed a higher rate of grade 3/4 myalgia than the TCb group (7% and 4.44%, respectively, p=0.363). To conclude, the TCb regimen can be used as an alternative regimen for TOP2A-normal stage II-III breast cancer patients in neoadjuvant chemotherapy. However, in patients with node-positive tumors, EC-T is still recommended. Though no difference of grade 3/4 thrombocytopenia in two groups, grade 4 thrombocytopenia caused by the carboplatin-containing regimen should be taken seriously.

Objective: To investigate the application value of magnetic resonance-ultrasound fusion (MR-USF) guided transperineal prostate biopsy (TPPB) in the diagnosis of prostate cancer., Methods: Relevant data were collected retrospectively from 77 patients undergoing MR-USF guided TPPB (n = 22) or 12-core systematic prostate biopsy (SPB) (n = 55) in Binhai People's Hospital from May to July 2019 and statistically analyzed using the software Graphad Prism 7.0 and SPSS 22.0., Results: The patients were aged 51－91 (70.5 ± 9.7) years, with a mean PSA level of (35.1 ± 115.4) μg/L (1.02－959 μg/L) and an average prostate volume of (48.81 ± 38.4) cm3 (7.54－307.61 cm3). There were no statistically significant differences in age, PSA, and BMI between the two groups of patients (P > 0.05). Prostate cancer was confirmed in 31 of the cases, with a positive rate of 40.26% (31/77), significantly higher in the TPPB (45.45% ［10/22］ than in the SPB group (38.18% ［21/55］, P < 0.01). Based on the PI-RADS scores, the Gleason grade was also higher in the former than in the latter group., Conclusions: MR-USF guided TPPB can improve the biopsy performance. Whether it should be used is based on the patient's PSA level and PI-RADS scores.

Aim: Cancer-associated fibroblasts (CAFs) are closely related to epithelial-mesenchymal transition (EMT) and chemoresistance in various cancers. Patients & methods: Experiments in vivo and retrospective studies were applied to explore the role of CAFs in epithelial ovarian cancer (EOC). Results: We found that CXCL12 expression was significantly increased in interstitial CAFs by immunofluorescence. CAF-derived CXCL12 induced EMT though CXCR4/Wnt/β-catenin pathway in EOC cells. Inhibited EMT led to increased apoptosis and cisplatin sensitivity. Multivariate regression analysis shows that CXCL12 expression in the stromal cells and cytoreduction satisfaction are independent prognostic markers of platinum-containing chemotherapy sensitivity in 296 EOC patients. Conclusion: CAFs may activate the Wnt/β-catenin pathway in EOC cells via CXCL12/CXCR4 axis, and then induce EMT and cisplatin resistance.

Background and Aims: Male breast cancer is an uncommon disease. The benefit of adjuvant chemotherapy in the treatment of male breast cancer patients has not been determined. The aim of this study was to explore the value of adjuvant chemotherapy in men with stage I-III breast cancer, and we hypothesized that some male patients may safely skip adjuvant chemotherapy., Methods: Male breast cancer patients between 2010 and 2015 from the Surveillance Epidemiology and End Results database were included. Univariate and multivariate Cox analyses were used to analyse the factors associated with survival. The propensity score matching method was adopted to balance baseline characteristics. Kaplan-Meier curves were used to evaluate the impacts of adjuvant chemotherapy on survival. The primary endpoint was survival., Results: We enrolled 514 patients for this study, including 257 patients treated with chemotherapy and 257 patients without. There was a significant difference in overall survival (OS) but not in breast cancer-specific survival (BCSS) between the two groups ( p  < 0.001 for OS and p  = 0.128 for BCSS, respectively). Compared with the non-chemotherapy group, the chemotherapy group had a higher 4-year OS rate (97.5% versus 95.2%, p  < 0.001), while 4-year BCSS was similar (98% versus 98.8%, p  = 0.128). The chemotherapy group had longer OS than the non-chemotherapy group among HR+, HER2-, tumour size >2 cm, lymph node-positive male breast cancer patients ( p  < 0.05). Regardless of tumour size, there were no differences in OS or BCSS between the chemotherapy and non-chemotherapy cohorts for lymph node-negative patients (OS: p  > 0.05, BCSS: p  > 0.05). Adjuvant chemotherapy showed no significant effects on both OS and BCSS in patients with stage I (OS: p  = 0.100, BCSS: p  = 0.858) and stage IIA breast cancer (OS: p  > 0.05, BCSS: p  > 0.05)., Conclusion: For stage I and stage IIA patients, adjuvant chemotherapy could not improve OS and BCSS. Therefore, adjuvant chemotherapy might be skipped for stage I and stage IIA male breast cancer patients., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Microbial contamination, especially in large-scale processes, is partly a life-or-death issue for industrial fermentation. Therefore, the aim of this research was to create an antimicrobial contamination system in Bacillus subtilis 168 (an ideal acetoin producer for its safety and acetoin synthesis potential). First, introduction of the formamidase (FmdA) from Helicobacter pylori and the phosphite dehydrogenase (PtxD) from Pseudomonas stutzeri enabled the engineered Bacillus subtilis to simultaneously assimilate formamide and phosphite as nitrogen (N) and phosphorus (P) sources. Thus, the engineered B. subtilis became the dominant population in a potentially contaminated system, while contaminated microbes were starved of key nutrients. Second, stepwise metabolic engineering via chromosome-based overexpression of the relevant glycolysis and acetoin biosynthesis genes led to a 1.12-fold increment in acetoin titer compared with the starting host. Finally, with our best acetoin producer, 25.56 g/L acetoin was synthesized in the fed-batch fermentation, with a productivity of 0.33 g/L/h and a yield of 0.37 g/g under a nonsterilized and antibiotic-free system. More importantly, our work fulfills many key criteria of sustainable chemistry since sterilization is abolished, contributing to the simplified fermentation operation with lower energy consumption and cost.

Background: Recent evidence suggests that albumin-to-Alkaline Phosphatase Ratio (AAPR) functions as a novel prognostic marker in several malignancies. However, whether it can predict the prognosis of unresectable pancreatic ductal adenocarcinoma (PDAC) remains unclear. Herein, we seek to investigate this possibility by a propensity score matching (PSM) analysis., Methods: This was a retrospective cohort study in which 419 patients diagnosed with unresectable PDAC and receiving chemotherapy were recruited. Patients were stratified based on the cutoff value of AAPR. The PSM analysis was performed to identify 156 well-balanced patients in each group for overall survival (OS) comparison and subgroup analysis. Univariate and multivariate analyses were carried out to examine the potential of AAPR to indicate the prognosis of unresectable PDAC. The prediction performance of conventional model and combined model including AAPR was compared using the Akaike Information Criterion (AIC) and concordance index (C-index)., Results: We identified an AAPR of 0.4 to be the optimal cutoff for OS prediction. Patients with AAPR≤0.4 had significantly shorter OS compared with patients with AAPR> 0.4 (6.4 versus 9.3 months; P < 0.001). Based on the PSM cohort and entire cohort, multivariate Cox analysis revealed that high pretreatment for AAPR was an independent marker predicting favorable survival in unresectable PDAC (hazard ratio, 0.556; 95% confidence interval, 0.408 to 0.757; P < 0.001). Significant differences in OS were observed in all subgroups except for the group of patients age ≤ 60. Combined prognostic model including AAPR had lower AIC and higher C-index than conventional prognostic model., Conclusions: Pretreatment AAPR servers as an independent prognostic indicator for patients with unresectable PDAC. Inclusion of AAPR improved the prediction performance of conventional prognostic model, potentially helping clinicians to identify patients at high risk and guide individualized treatment.

The overall risk of developing a second primary cancer is increasing. The purpose of this study was to analyze the survival of patients with breast cancer diagnosed after a prior cancer and identify risk factors of breast cancer death in this population. Using the SEER database, we identified 1,310 woman diagnosed with breast cancer between 2010 and 2015 after a prior cancer as the primary cohort. Clinicopathological characteristics were compared using the Student t -test and chi-square test. Fine and Gray's regression was used to evaluate the effect of treatments on breast cancer death. After propensity score matching (PSM), 9,845 pairs of patients with breast cancer as the prior or second cancer diagnosed between 2010 and 2011 were included as a second cohort. PSM-adjusted Kaplan-Meier and Cox hazards models were used to evaluate the impact of prior cancer on survival. The results showed that survivors of gynecologic cancers (e.g., ovarian cancer) had a higher risk of developing breast cancer than survivors of gastrointestinal and urinary tract cancers. More patients died of breast cancer than of prior urinary cancer (53.3% vs. 40%, P < 0.05) and melanoma (66.7% vs. 33.3%, P < 0.05). The ratio of breast cancer deaths to prior cancer deaths was significantly higher in patients with diagnoses interval ≥ 3 years than in those with the interval < 3 years (2.67 vs. 0.69, P < 0.001). Breast cancer-specific survival and overall survival rates were significantly lower in women with breast cancer as the second primary cancer than in those with breast cancer as the prior cancer, especially among hormone receptor-positive women. However, breast cancer treatment decreased the risk of breast cancer -specific death (hazard ratio = 0.695, 95% confidence interval: 0.586-0.725, P < 0.001). Breast cancer patients with prior cancers must be carefully considered for clinical trials.

Chemokines play essential roles in the progression of various human cancers; however, the expression and role of CXC chemokines in pancreatic adenocarcinoma (PAAD) have not yet been identified. The aim of this study is to identify the expression patterns, clinical significance and mechanisms of CXC chemokines in regulating tumour microenvironment of PAAD. Three CXC chemokines, including CXCL5, CXCL9, and CXCL10, were significantly overexpressed in PAAD tissues, which were correlated with the poor survival of the patients. CXCL9/10 was associated with change of immune cell pattern in the tumour microenvironment, and supplementation of CXCL9 in the orthotopic murine PAAD model promoted tumour progression. In particular, CXCL9 reduced the CD8+ cytotoxic T lymphocytes in the tumour microenvironment of PAAD, which could be attributed to the reduced CD8+ T cell proliferation, activation, and secretion of anti-tumour cytokines. In vitro treatment of CXCL9 directly led to the suppression of the proliferation, activation, and secretion of anti-tumour cytokines of isolated CD8+ T cells. Inhibition of STAT3 recovered the CXCL9-inhibited proliferation, activation, and secretion of anti-tumour cytokines of CD8+ T cells. Our study indicates CXCL9 as a potential target of immunotherapy in PAAD treatment by regulating the CD8+ T lymphocytes in the tumour microenvironment.

Pancreatic cancer is a highly malignant tumor of the digestive system. Previous studies have shown that abnormal cell surface glycosylation is associated with cancer metastasis, which suggests that glycosylation changes may open a new window for discovering metastasis-related pathways. In this study, we used a microarray with 55 lectins to screen for altered glycosylation between two metastatic pancreatic cancer lines (Capan-1 and Su.86.86) and two nonmetastatic pancreatic cancer lines (Panc-1 and MIA PaCa-2), and we further analyzed three lectins with high-binding activities (AAL, UEA-I, and PHA-E) in cell motility assays using these pancreatic cancer cells to detect whether blocking certain forms of cell surface glycosylation affects any processes associated with metastasis. As a result, we found that AAL, a fucose-specific lectin, has different binding patterns between metastatic pancreatic cancer and nonmetastatic pancreatic cancer lines and inhibits cell motility in metastatic pancreatic cancer cells. Furthermore, the N-fucosylation-related genes FUT3, 5, and 6 were found to be responsible for the elevated fucosylation in metastatic pancreatic cells through real-time PCR screening. In summary, our findings that the specific bindings of AAL on cell surfaces and highly expressed FUT3, 5, and 6 in metastatic pancreatic cancer cells, although preliminary, are encouraging, and our established combined method is also suitable for discovering metastasis-related mechanisms in other cancers., (Copyright © 2019. Published by Elsevier Inc.)

Objective: The aim of this study was to evaluate the prognostic value of pre-treatment plasma hemostatic parameters in patients with advanced pancreatic cancer., Methods: A total of 320 patients diagnosed with advanced pancreatic cancer between January 1, 2011 to December 31, 2015 were enrolled in this retrospective study. The prognostic significance of hemostatic parameters such as prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FBG), platelet count (PLT), mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW) was determined by univariate and multivariate Cox hazard models. Then, Kaplan-Meier methods and log-rank tests were performed to compare the survival of patients in different risk groups., Result: Univariate and multivariate analyses showed that prolonged PT, high FBG, and high MPV were independent prognostic factors for poor overall survival (PT > 11.3 s, HR = 1.46, 95%CI = 1.10-1.94, p = 0.009; FBG>2.5 g/L, HR = 1.41, 95%CI = 1.08-1.84, p = 0.011; MPV>12.2 fL, HR = 1.52, 95%CI = 1.13-2.04, p = 0.005). Moreover, all the patients were stratified into three groups by a scoring system based on these three hemostatic markers. The median survival time of the three groups was 8.8 months, 6.3 months and 4.3 months (P < 0.001)., Conclusion: PT, FBG and MPV were independent prognostic factors in advanced pancreatic cancer. A novel scoring system based on these hemostatic parameters could be used to predict the survival of patients with advanced pancreatic cancer., (Copyright © 2018. Published by Elsevier B.V.)

Mycobacterium tuberculosis (Mtb) serine/threonine kinase PknG plays an important role in the Mtb-host interaction by facilitating the survival of Mtb in macrophages. However, the human proteins with which the PknG interacts, and the underlying molecular mechanisms are still largely unknown. In this study, a HuProt array is been applied to globally identify the host proteins to which PknG binds. In this way, 125 interactors are discovered, including a cyclophilin protein, CypA. This interaction between PknG and CypA is validated both in vitro and in vivo, and functional studies show that PknG significantly reduces the protein levels of CypA through phosphorylation, which consequently inhibit the inflammatory response through downregulation of NF-κB and ERK1/2 pathways. Phenotypically, overexpression of PknG reduces cytokine levels and promotes the survival of Mycobacterium smegmatis (Msm) in macrophages. Overall, it is expected that the PknG interactors identified in this study will serve as a useful resource for further systematic studies of the roles that PknG plays in the Mtb-host interactions., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: The prognostic value of the mesenchymal-epithelial transition (MET) in triple-negative breast cancers (TNBCs) remains controversial. A meta-analysis of the impact of MET in TNBCs was performed by searching published data., Methods: PubMed and Embase databases were searched for eligible literature. The principal outcome measures were hazard ratios (HRs) for recurrence-free survival or overall survival according to MET expression. Combined HRs were calculated using fixed- or random-effects models according to heterogeneity., Results: Six studies involving 785 patients met our selection criteria. The meta-analysis results showed that MET overexpression was associated with a 1.29-fold increased risk of recurrence (combined HR 1.29; 95% confidence interval, 1.04-1.60; P = .020) in the TNBCs. Three studies provided the related overall survival data (488 cases). The results showed that MET overexpression was associated with a 1.38-fold increased risk of mortality (HR, 1.38; 95% confidence interval, 1.08-1.76; P = .009)., Conclusion: MET is an adverse prognostic marker for TNBCs. The results strengthen the rationale for targeted therapy of TNBCs using MET inhibitors in future clinical trials., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) is a chronic hepatic disease associated with excessive accumulation of lipids in hepatocytes. As the disease progresses, oxidative stress plays a pivotal role in the development of hepatic lipid peroxidation. Cytochrome P450 1A1 (CYP1A1), a subtype of the cytochrome P450 family, has been shown to be a vital modulator in production of reactive oxygen species. However, the exact role of CYP1A1 in NAFLD is still unclear. The aim of this study was to investigate the effects of CYP1A1 on lipid peroxidation in oleic acid (OA)-treated human hepatoma cells (HepG2). We found that the expression of CYP1A1 is elevated in OA-stimulated HepG2 cells. The results of siRNA transfection analysis indicated that CYP1A1-siRNA inhibited the lipid peroxidation in OA-treated HepG2 cells. Additionally, compared with siRNA-transfected and benzo[a]pyrene (BaP)-OA-induced HepG2 cells, overexpression of CYP1A1 by BaP further accelerated the lipid peroxidation in OA-treated HepG2 cells. These observations reveal a regulatory role of CYP1A1 in liver lipid peroxidation and imply CYP1A1 as a potential therapeutic target.

Brain metastatic triple negative breast cancer (BM-TNBC) is afflicted with unfavorable prognosis. However, the molecular events underlying BM-TNBC remain largely unknown. In the present study, we conducted gene expression microarray analysis using the triple negative breast cancer cell line MDA-MB-231 and its brain metastatic derivative (MDA-MB-231Brm). Results of microarray analysis showed that a total of 4296 genes were differentially expressed, of which 2433 genes were up-regulated and 1863 genes were down-regulated. Gene Ontology (GO), KEGG pathway and protein-protein interaction (PPI) analyses indicated differentially expressed genes functionally categorized as genes of signal transduction, multicellular organismal development, ion transport, nervous system development, plasma membrane, extracellular region, calcium ion binding, GTP binding neuroactive ligand-receptor interaction. The validity of the microarray results was verified by quantitative real-time PCR analysis of twelve representative genes. The present findings revealed molecular basis and events associated with brain metastasis in TNBC, which will potentially contribute to the understanding of underlying mechanism and develop therapeutic targets., (Copyright © 2017. Published by Elsevier B.V.)

Objective: Tumor necrosis factor superfamily member 9 (TNFSF9), also known as 4-1BBL and CD137L, has been implicated in cancer immunotherapy due to its function as a T-cell co-stimulator. We aimed to investigate the role of TNFSF9 in the cancer pathogenesis in hepatocellular carcinoma (HCC)., Methods: TNFSF9 expression was examined by immunohistochemistry in 106 pairs of HCC and adjacent non-tumorous tissues, and by quantitative polymerase chain reaction and Western blot in HCC cell lines. The impact of TNFSF9 on the proliferation, migration and invasion of HCC cells was determined using the 3-(4,5-diethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) and transwell assays in vitro. We also assessed the influence of TNFSF9 on the growth and metastasis of HCC tumors in an orthotopic mouse model of human HCC., Results: TNFSF9 expression was downregulated in approximately 70% of HCC tissues. A decreased expression of TNFSF9 was also consistently observed in all the four HCC cell lines. Either the overexpression of TNFSF9 or treatment with recombinant TNFSF9 protein could significantly inhibit the proliferation, migration and invasion of Huh7 and SMMC-7721 HCC cells in vitro. The inhibitory effect of TNFSF9 on HCC was further confirmed in vivo. Mice orthotopically transplanted with TNFSF9-overexpressing Huh7 cells developed significantly smaller tumors with less intrahepatic metastasis and distant metastasis compared with the control group., Conclusions: TNFSF9 may be a tumor suppressor in HCC. Based on its immune stimulatory aspect and the tumor inhibition property, TNFSF9 may be a promising therapeutic target for HCC., (© 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Immunohistochemistry (IHC) and fluorescent in situ hybridization are reliable methods for identifying c-Met protein expression or c-Met gene amplification. However, each technique requires a high-quality tissue sample, which might not be available. The aim of the present study was to investigate the correlation between the soluble c-Met level and tissue c-Met protein expression and the relationship between these markers and patient prognosis., Materials and Methods: In 198 patients with advanced non-small-cell lung cancer, tumor tissue c-Met expression was determined using IHC according to the H score criteria. Positivity was defined as ≥ 50% of cells with strong staining (IHC 3+). The concentration of c-Met protein in paired plasma samples was measured using a human soluble c-Met quantitative enzyme-linked immunosorbent assay kit, and the predictive value was determined using receiver operating characteristic curve analysis., Results: Of the 198 patients, 140 (70.7%) had tissue c-Met - findings and 58 (29.3%) tissue c-Met + findings. Receiver operating characteristic curve analysis showed 67.2% specificity and 65.0% sensitivity for predicting tissue c-Met positivity at a plasma c-Met cutoff of 766 ng/mL. The correlation between the soluble c-Met level and tissue c-Met protein expression was significant (Pearson's r = 0.309; P < .001). Patients with high soluble c-Met levels (> 766 ng/mL) had poorer overall survival than patients with low soluble c-Met levels (9.5 vs. 22.2 months; P < .001). Multivariate analyses demonstrated the same result (hazard ratio, 2.15; 95% confidence interval, 1.334-3.446; P = .002)., Conclusion: A significant correlation was found between the plasma soluble c-Met levels and tissue c-Met protein expression in patients with advanced non-small-cell lung cancer. A high level of soluble c-Met was associated with a poor prognosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Predictive biomarkers of mesenchymal-to-epithelial transition factor (MET)-targeted therapy remain elusive. Since the discovery of the MNNG HOS Transforming gene (MET) exon 14 mutation, it has been found to have the best potential to become one precise biomarker for MET-targeted therapy. Here, we present the unique characteristics of MET exon 14 mutations in Chinese patients with NSCLC., Methods: A total of 1296 patients with NSCLC were screened for MET exon 14 mutations. Next-generation sequencing was performed on the DNA of 968 patients and Sanger sequencing was conducted on complementary DNA of the other 328 patients. Immunohistochemical analysis and fluorescence in situ hybridization were also performed on all specimens., Results: Twelve patients had MET exon 14 mutations. These accounted for only 0.9% of adenocarcinoma. Thus, the mutations were present at less than half the frequency of their occurrence in Western patients (0.9% versus 3% in Chinese and white patients, respectively, χ(2) = 15.1, p < 0.001). Samples from six patients with MET exon 14 mutations were analyzed using immunohistochemical analysis and fluorescence in situ hybridization. We found no significant relationships among the mutation, MET amplification, and MET overexpression. In two patients who received crizotinib, only one patient (who exhibited MET amplification) experienced a partial response; the progression-free survival was 9 months. However, it remains unclear whether the sensitivity of this patient to crizotinib was conferred by the MET exon 14 mutation per se or by MET amplification. In the other patient with concomitant MET exon 14 skipping and KRAS G12D mutation, the disease progressed in only 1 month., Conclusions: MET exon 14 mutation per se may not be sufficiently robust for use in defining a subset of NSCLCs. Further research on MET exon 14 mutations, MET amplification, and MET overexpression is required. Maybe a panel of biomarkers will be necessary in the future., (Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

MET overexpression and the EGFR T790M mutation are both associated with acquired resistance (AR) to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC). We characterized the frequency, underlying molecular mechanisms, and subsequent treatment for AR in MET overexpressing NSCLC patients with or without the T790M mutation. The study participants were 207 patients with advanced NSCLC and AR to EGFR-TKIs. The percentages of MET-, T790M- and MET/T790M-positive patients were 20.3% (42/207), 34.8% (72/207) and 6.8% (14/207), respectively. The disease control rate was 100% (5/5) for five patients with MET overexpression who received EGFR-TKIs plus a MET inhibitor. Among the MET/T790M-positive patients, seven received EGFR-TKIs plus a MET inhibitor and four received a T790M inhibitor, but no response was observed. The median post-progression survival (PPS) was 14.1, 24.5, and 10.7 months for MET-overexpressing, T790M-positive and MET/T790M-positive patients, respectively (P=0.044). c-Met, p-Met, ERBB3, and p-ERBB3 were highly expressed in MET-positive and MET/T790M-positive patients, but were poorly expressed in T790M-positive patients. EGFR, p-EGFR, AKT, p-AKT, MAPK, and p-MAPK were highly expressed in all three groups. These results suggest that MET/T790M-positive patients are at higher risk of AR to EGFR-TKIs, and have a worse PPS than patients with only MET overexpression or the T790M mutation alone. Clinical trials are needed to determine the best treatment for patients with both MET overexpression and the EGFR T790M mutation., Competing Interests: All authors have declared no conflicts of interest.

Avascular necrosis of femoral head (AVFH) is a clinically recalcitrant disease of hip that leads to joint destruction. Osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B (RANK) and RANK ligand (RANKL) regulates the balance, maturation and function of osteoclast and bone remodeling. This study aims to investigate molecular pathways which leads to AVN by studying expression profile of OPG, RANK and RANKL genes. Quantitative Real Time-PCR is used to evaluate mRNA expression of OPG, RANK and RANKL. mRNA and protein level in normal and necrotic tissue from 42 samples of ANFH specimens were analyzed. OPG and RANKL protein levels are estimated by western blotting. The results indicated that OPG mRNA levels are higher but not significantly different in necrotic tissue than that in normal tissue (P>0.05). Although expression of RANK and RANKL is significantly lower than that of OPG, RANK and RANKL mRNA levels are higher in necrotic tissue than normal tissue (P<0.05). Protein levels of OPG and RANKL show no significant difference. In conclusion, OPG, RANK and RANKL play important role in progress of bone remodeling in necrotic area and in disturbance of bone homeostasis, which might have an effect on bone destruction and subsequent collapse of hip joint.

Background: The activation of c-Met has been associated with both primary and acquired resistance to EGFR-TKI therapy in NSCLC patients. Thus, c-Met status during EGFR-TKI therapy should receive much attention., Results: Forty-nine patients were selected as training cohort and 52 cases as validation cohort. With disease progression, IHC results showed that 37 (75.5%) of the patients were tissue c-Met-negative, and 12 (24.5%) were tissue c-Met-positive. There was a statistically significant difference in the dynamic change in soluble c-Met between the tissue c-Met-negative and c-Met-positive groups (P = 0.002). Patients with a baseline soluble c-Met level >766 ng/ml showed inferior median progression-free survival (PFS; 10.2 vs. 14.0 months; P = 0.003) after EGFR-TKI treatment. Multivariate Cox proportional hazards model analyses demonstrated that the soluble c-Met level was an independent prognostic factor for PFS after EGFR-TKI treatment (P = 0.009; hazard ratio: 3.583; 95% confidence interval: 1.379-9.312). In the validation cohort, patients with soluble c-Met levels >766 ng/ml were also determined to have significant short median PFS after EGFR-TKI treatment (6.8 vs. 14.5 months, P < 0.001)., Patients and Methods: We retrospectively investigated the dynamic change in the soluble c-Met level in plasma and its relationship with clinical outcomes of EGFR-TKI therapy in advanced NSCLC. Immunohistochemistry (IHC) was used to assess the expression of c-Met in the resistant tissue. Plasma c-Met levels were assayed in duplicate using a human soluble c-Met quantitative enzyme-linked immunosorbent assay (ELISA) kit., Conclusions: Quantitatively determining the soluble c-Met level in plasma by ELISA might provide a non-invasive and sensitive method to predict EGFR-TKI prognosis., Competing Interests: The authors have declared that no competing interests exist.