The Relationship Between the Molecular Phenotypes of Brain Gliomas and the Imaging Features and Sensitivity of Radiotherapy and Chemotherapy.

Gliomas are the most common primary malignant tumors of the brain, accounting for about 80% of all central nervous system malignancies. With the development of molecular biology, the molecular phenotypes of gliomas have been shown to be closely related to the process of diagnosis and treatment. The molecular phenotype of glioma also plays an important role in guiding treatment plans and evaluating treatment effects and prognosis. However, due to the heterogeneity of the tumors and the trauma associated with the surgical removal of tumor tissue, the application of molecular phenotyping in glioma is limited. With the development of imaging technology, functional magnetic resonance imaging (MRI) can provide structural and function information about tumors in a noninvasive and radiation-free manner. MRI is very important for the diagnosis of intracranial lesions. In recent years, with the development of the technology for tumor molecular diagnosis and imaging, the use of molecular phenotype information and imaging procedures to evaluate the treatment outcome of tumors has become a hot topic. By reviewing the related literature on glioma treatment and molecular typing that has been published in the past 20 years, and referring to the latest 2020 NCCN treatment guidelines, summarizing the imaging characteristic and sensitivity of radiotherapy and chemotherapy of different molecular phenotypes of glioma. In this article, we briefly review the imaging characteristics of different molecular phenotypes in gliomas and their relationship with radiosensitivity and chemosensitivity of gliomas.

[The effects of high risk of ovarian hyperstimulation syndrome and duration of embryo cryopreservation on perinatal outcomes of single live births in the first frozen embryo transfer cycle after whole embryo cryopreservation].

Objective: To investigate the effects of high risk of ovarian hyperstimulation syndrome (OHSS) and duration of embryo cryopreservation on perinatal outcomes of the first frozen-thawed cycle after whole embryo cryopreservation. Methods: The clinical data of 1 804 patients who underwent the first frozen-thawed cycle after whole embryo cryopreservation and achieved singleton live births in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to June 2021 were retrospectively analyzed. According to whether there was high risk of OHSS in the oocyte retrieval cycle, the patients were divided into high-risk group (n=790) and non-high-risk group (n=1 014). The baseline data and perinatal outcomes were compared between the two groups. Multivariate linear regression was applied to analyze the relative factors affecting neonatal weight. And the high-risk group was divided into three subgroups according to different cryopreservation time: the embryos of 96 cycles with a cryopreservation time less than 60 days were defined as group A; the embryos of 587 cycles with a cryopreservation time around 60 to 120 days were defined as group B; the embryos of 107 cycles with a cryopreservation time more than 120 days were defined as group C. The perinatal outcomes were compared among the three groups. The measurement data in this study were represented byï¼»M（Q1，Q3）］. Results: The female age in the high-risk group was 30.0 (27.0, 32.0) years old, which was lower than that in the non-high-risk group 31.0 (29.0, 34.0) (P<0.001). The male age in high-risk group was 30.0 (28.0, 33.0), lower than that in non-high-risk group 32.0 (29.0, 35.0) (P<0.001). The birth weight of high-risk group [3 500.0 (3 200.0,3 800.0) g] was higher than that of control group [3 400.0 (3 150.0,3 800.0) g](P=0.045). Multivariate linear regression analysis showed that female BMI was correlated with neonatal weight, ß (95%CI) was 15.37(8.33, 22.41) (P<0.001), and the high risk of OHSS was not correlated with neonatal weight, ß (95%CI) was 19.40 (-38.07, 76.87) (P=0.508). There was significant difference in the incidence of low birth weight and very low birth weight among groups A, B and C (all P values<0.05), and the incidence of low birth weight and very low birth weight in group C was higher than that in group B (all P values<0.017). Conclusions: The risk of adverse perinatal outcomes in high-risk OHSS patients who underwent the first frozen-thawed cycle after whole embryo cryopreservation was not increased. However, prolonged cryopreservation of embryos may lead to increased risk of low birth weight and very low birth weight.

[Effect of pelvic peritoneum reconstruction on the prognosis of patients underwent laparoscopic low anterior resection of rectal adenocarcinoma].

Objective: To investigate the effect of pelvic peritoneum reconstruction on the prognosis of patients underwent laparoscopic low anterior resection of rectal adenocarcinoma. Methods: This retrospective cohort study included 97 patients who underwent laparoscopic low anterior resection of rectal adenocarcinoma in General Surgery Department, the First Affiliated Hospital of Soochow University from January 2017 to June 2021. According to the implementation of pelvic peritoneum reconstruction, the subjects were divided into study group (48 patients underwent pelvic peritoneum reconstruction after laparoscopic resection) and control group (49 patients not underwent pelvic peritoneum reconstruction). The two groups were compared in terms of Wexner score of anal function, anorectal manometry results, normal rate of defecation sensation, pelvic floor anatomical structure and postoperative complications. Five-year survival analysis was performed. Results: Patients in the study group and the control group were (61.25±10.38) years old and (59.47±11.40) years old (P>0.05). The proportions of male patients were 60.4% (29 cases) and 55.1% (27 cases) (P>0.05) in the study group and control group, respectively. At 3, 6 and 12 months after surgery, Wexner scores of anal function in the study group were lower than those in the control group [(14.29±2.07) vs (16.33±2.18), P<0.001; (9.57±2.34) vs (11.26±2.85), P=0.002; (5.41±1.36) vs (7.86±1.95), P<0.001, respectively]. The anal resting pressure and anal systolic pressure of the study group were higher than those of the control group [(56.29±7.31) mmHg vs (52.88±6.65) mmHg, P=0.018; (129.33±17.36) mmHg vs (110.45±15.22) mmHg, P<0.001, respectively] (1 mmHg=0.133 kPa). The rectal sensory volume, rectal maximum tolerance volume, and the length of anal high-pressure area in the study group were greater than those in the control group [(32.15±4.38) vs (29.76±4.29), P=0.008; (209.57±40.27) vs (184.39±37.56), P=0.002; (3.07±0.52) vs (2.80±0.49), P=0.010, respectively]. At 3 and 6 months after surgery, the normal rates of defecation sensation in the study group were 47.9% (23 cases) and 70.8% (34 cases), respectively, higher than those in the control group [26.5% (13 cases) and 51.0% (25 cases)] (P=0.029 and 0.046, respectively). The detection rate of intestinal tube accumulation in the study group was lower than that in the control group [12.5% (6 cases) vs 38.9% (19 cases)] (P=0.003). There was no significant difference in the total incidence of complications (anastomotic leakage, abdominal infection, intestinal obstruction, pendant pneumonia and urinary tract infection) between the two groups [18.8% (9 cases) vs 24.5% (12 cases)] (P=0.493). There was no significant difference in 5-year cumulative survival rate between the study group and the control group (71.6% vs 68.2%, P=0.309). Conclusion: Pelvic peritoneum reconstruction can improve postoperative anal function and reduce intestinal tube accumulation in patients underwent laparoscopic low anterior resection of rectal adenocarcinoma with high safety and feasibility.

[Clinical features and prognosis of anastomotic leak after anterior resection for rectal cancer following neoadjuvant chemoradiotherapy].

Objective: To explore clinical features and prognosis of anastomotic leak (AL) after anterior resection following neoadjuvant chemoradiotherapy for rectal cancer patients. Methods: A retrospective cohort study was performed. Data were retrieved from colorectal cancer database of the Sixth Affiliated Hospital, Sun Yat-sen University. The clinical data of 470 patients with rectal cancer who underwent anterior resection after neoadjuvant chemoradiotherapy at our department from September 2010 to December 2018 were enrolled. Clinical features and outcome of postoperative AL were analyzed. The primary outcomes were the short-term and long-term incidence and severity of AL (ISREC grading standard was adopted). The secondary outcomes were the prognostic indicators of AL, including the secondary chronic presacral sinus, anastomotic stenosis and persistent stoma. Patients received regular follow-up every 3-6 months after surgery, including physical examination, blood test, colonoscopy and image; those received follow-up once a year after postoperative 2-year; those who did not return to our hospital received telephone follow-up. Data of this study were retrieved up to January 2020. Univariate χ(2) test and multivariate logistic analysis were used to identify risk factors of AL and prognostic factors of persistent stoma. Results: There were 331 males (70.4%) with the average age of (53.5±11.6) years. Distance from tumor to anal verge ≤ 5 cm was found in 228 (48.5%) patients. The diverting stoma was performed in 440 (93.6%) patients. After a median follow-up of 28 months, AL was found in 129 (27.4%) patients, including 67 (14.3%) patients with clinical leak (ISREC grade B-C). The median time for diagnosis of AL was 70 days (2-515 days) after index surgery. Common symptoms included sacrococcygeal pain (27.9%, 36/129), purulent discharge through anus (25.6%, 33/129), and rectal irritation (17.8%, 23/129). Sixty five point one percent (84/129) of the defect site was at the posterior wall of the anastomosis. Transanal incision and drainage or lavage (27.9%, 36/129) and percutaneous drainage under ultrasound or CT (17.1%, 22/129) were the most common management. Chronic presacral sinus tract could not be evaluated in 12 patients because imaging was performed more than 1 year after the operation. Evaluation beyond 1 year showed that 73 of 458 eligible patients (15.9%) were found with chronic presacral sinus, accounting for 62.4% (73/117) of patients with AL; 69 of 454 (15.2%) were diagnosed with anastomotic stenosis, of whom 49 were secondary to AL; 59 of 470 (12.6%) had persistent stoma due to AL. Univariate analysis showed that male, operative duration > 180 minutes, intraoperative blood loss >150 ml, and pelvic radiation injury were associated with AL (all P<0.05). Multivariate analysis showed that male (OR=1.72, 95% CI: 1.04-2.86, P=0.036), intraoperative blood loss > 150 ml (OR=1.82, 95% CI: 1.11-2.97, P=0.017), and pelvic radiation injury (OR=4.90, 95% CI: 3.09-7.76, P<0.001) were independent risk factors of AL after anterior resection. For patients with AL, clinical leak (ISREC grade B-C) (OR=9.59, 95% CI: 3.73-24.69, P<0.001), age ≤55 years (OR=3.35, 95% CI: 1.35-8.30, P=0.009), distance from tumor to anal verge ≤ 5 cm (OR=3.33, 95% CI: 1.25-8.92, P=0.017), and pelvic radiation injury (OR=3.29, 95% CI: 1.33-8.14, P=0.010) were independent risk factors of persistent stoma. Conclusions: AL after anterior resection following neoadjuvant chemoradiotherapy for rectal cancer patients is common. Among patients with AL, the proportion of those needing persistent stoma is high. Pelvic radiation injury is significantly associated with occurrence of AL and subsequent persistent stoma. Sphincter-preserving surgery for rectal cancer should be selectively used based on the risk of pelvic radiation injury, which is beneficial to reduce the incidence of AL and improve the quality of life.

Pediatric allergic rhinitis with functional gastrointestinal disease: Associations with the intestinal microbiota and gastrointestinal peptides and therapeutic effects of interventions.

Children are susceptible to allergic rhinitis (caused by external allergens) accompanied by functional gastrointestinal disease, which seriously affects physical and mental health. Antihistamines and nasal spray hormones are commonly used in clinical treatment, but these drugs often have unsatisfactory efficacy and result in high recurrence rates. Therefore, understanding the pathogenesis of allergic rhinitis with functional gastrointestinal disease and seeking safer treatment and prevention methods is essential. Herein, molecular ecology and immunoassays were used to analyze correlations between pediatric allergic rhinitis with functional gastrointestinal disease and both the intestinal microbiota and gastrointestinal peptide levels. Fifty healthy children (healthy group) and 80 children with allergic rhinitis with functional gastrointestinal disease (case group: evenly divided into a control group (conventional drug therapy) and an intervention group (conventional drug therapy + glutamine+probiotics)), were enrolled. Bifidobacterium and Lactobacillus counts and the gastrin and motilin levels were lower in the case group than in the healthy group, whereas Enterobacter, yeast, and Enterococcus counts and the somatostatin, serotonin, and vasoactive intestinal peptide levels were higher. Post treatment, intestinal microbiota indices, gastrointestinal peptide levels, and intestinal barrier function were better in the intervention group than in the control group (p < 0.05). The intervention group had a significantly higher total therapeutic response rate (95.00%) than the control group (77.50%). The intestinal microbiota was closely associated with gastrointestinal peptide levels. Treatment with glutamine and probiotics regulated these levels, re-established balance in the intestinal microbiota, and restored intestinal barrier function.

Extracellular Vesicles Derived from Neural Progenitor Cells--a Preclinical Evaluation for Stroke Treatment in Mice.

Stem cells such as mesenchymal stem cells (MSCs) enhance neurological recovery in preclinical stroke models by secreting extracellular vesicles (EVs). Since previous reports have focused on the application of MSC-EVs only, the role of the most suitable host cell for EV enrichment and preclinical stroke treatment remains elusive. The present study aimed to evaluate the therapeutic potential of EVs derived from neural progenitor cells (NPCs) following experimental stroke. Using the PEG technique, EVs were enriched and characterized by electron microscopy, proteomics, rt-PCR, nanosight tracking analysis, and Western blotting. Different dosages of NPC-EVs displaying a characteristic profile in size, shape, cargo protein, and non-coding RNA contents were incubated in the presence of cerebral organoids exposed to oxygen-glucose deprivation (OGD), significantly reducing cell injury when compared with control organoids. Systemic administration of NPC-EVs in male C57BL6 mice following experimental ischemia enhanced neurological recovery and neuroregeneration for as long as 3 months. Interestingly, the therapeutic impact of such NPC-EVs was found to be not inferior to MSC-EVs. Flow cytometric analyses of blood and brain samples 7 days post-stroke demonstrated increased blood concentrations of B and T lymphocytes after NPC-EV delivery, without affecting cerebral cell counts. Likewise, a biodistribution analysis after systemic delivery of NPC-EVs revealed the majority of NPC-EVs to be found in extracranial organs such as the liver and the lung. This proof-of-concept study supports the idea of EVs being a general concept of stem cell-induced neuroprotection under stroke conditions, where EVs contribute to reverting the peripheral post-stroke immunosuppression.

["Point line anterograde dissection" for the safe preparation of supraclavicular flap].

Objective: To investigate the application in the preparation of supraclavicular island flap by "point line anterograde dissection (PLAD) ". Methods: A retrospective analysis was performed on 45 flaps of 43 patients treated with supraclavicular artery island flap from the Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital Affiliated to Capital Medical University from January 2013 to June 2019. The patients were all male, aged 35-72 years old. There were 26 cases of hypopharyngeal cancer, 4 cases of recurrent laryngeal cancer, 2 cases of cervical esophageal cancer, 1 case of tonsillar cancer, 1 case of parotid gland cancer, 3 cases of postoperative pharyngeal fistula after hypopharyngeal cancer, 2 cases of esophageal fistula after trauma, 2 cases of esophageal stricture after hypopharyngeal carcinoma operation, 1 case of autoimmune laryngeal stenosis, and 1 case of cheek defect after maxillary sinus cancer operation."Point" was the origin of the supraclavicular artery in the transverse carotid artery. "Line" was an extension line made along the starting point of the supraclavicular vessel for anterograde anatomy of 1-2 cm and the direction of the blood vessel. The extension line was used as the central axis of the designed island flap. Characteristics of flap blood supply, the time of flap preparation, flap survival, donor area recovery and clinical follow-up were recorded. Results: The arterial blood supply of the flap was constant, and the venous reflux was variable. The area of the prepared flap was (4-8) cm×(10-18) cm, and the preparation time was 30-60 min, with a median of 42 min. Skin flap survival rate was 100%. Partial necrosis of skin flap occurred in 1 patient and postoperative pharyngeal fistula occurred in 5 patients, all of whom were cured by dressing change. The donor site defects were closed and sutured directly. 3 patients had partial incision dehiscence and healed after dressing change. During the follow-up, 1 patient was lost, and the remaining 42 patients were followed up for 8 to 55 months.40 patients involved swallowing function, all of them returned to regular diet or soft fluid after operation.40 patients involved malignant tumors and local tumor recurrence in 3 patients among whom, there were 2 cases of lymph node recurrence, and 2 cases of distant metastasis, including 1 case of lung metastasis and 1 case of bone metastasis. Conclusion: PLAD is a simple, safe and efficient method for the preparation of supraclavicular island flap.

Method to retrieve aerosol extinction profiles and aerosol scattering phase functions with a modified CCD laser atmospheric detection system.

Vertical distributions of ambient aerosols and their corresponding optical properties are crucial to the assessment of aerosol radiative effects. Traditionally, ambient aerosol phase function is assumed as a constant of input parameter in the retrieval of the vertical distribution of aerosol optical characteristics from remote sensing measurements (e.g. lidar or camera-laser based instruments). In this work, sensitivity studies revealed that using constant aerosol phase function assumptions in the algorithm would cause large uncertainties. Therefore, an improved retrieval method was established to simultaneously measure ambient aerosol scattering phase functions and aerosol scattering function profiles with a modified charge-coupled device-laser aerosol detection system (CLADS), which are then combined to yield vertical profiles of aerosol extinction coefficients. This method was applied and evaluated in a comprehensive field campaign in the North China Plain during January 2016. The algorithm showed robust performance and was able to capture temporal variations in ambient aerosol scattering phase functions and aerosol scattering function profiles. Aerosol extinction coefficients derived with simultaneously measured aerosol phase functions agreed well with in-situ measurements, indicating that uncertainties in the retrieval of aerosol extinction vertical profiles have been significantly reduced by using the proposed method with the modified CLADS. The advantage of this modified CLADS is that it can accomplish these aerosol measurements independent of other supplementary instruments. Benefiting from its low cost and high spatial resolution (∼1 m on average) in the boundary layer, this measurement system can play an important role in the research of aerosol vertical distributions and its impacts on environmental and climatic studies.

The impacts of gene polymorphisms on methotrexate in Chinese psoriatic patients.

BACKGROUND: Methotrexate (MTX) is the first-line treatment for psoriasis in China. The metabolic processes of MTX include various proteins and genes. Previous studies have shown that gene polymorphisms had significant impacts on the efficacy of MTX. However, the influence of gene polymorphisms has not been reported in the Chinese psoriatic patients. OBJECTIVE: The aim of this study was to verify the impacts of candidate genes polymorphisms on the effectiveness of MTX in a Chinese psoriatic population. METHODS: In this study, we enrolled 259 psoriasis patients from two clinical centres. Each of them received MTX treatment at 7.5-15 mg/week for at least 8 weeks. Patients were stratified as responders and non-responders according to whether the Psoriasis Area and Severity Index score declined more than 75% (PASI75). According to previous reports, 16 single nucleotide polymorphisms (SNPs) were selected and genotyped for each patient using the Sequenom platform. Fisher's exact test, the chi-square test, Mann-Whitney tests and ANOVA analyses were used for statistical analysis. RESULTS: Among 259 patients, there were 182 males and 77 females, 63 patients with psoriatic arthritis and 196 patients without arthritis phenotype, and the age of all patients ranged from 19 to 70 years (49.7 ± 13.6). The baseline PASI value of patients was 13.8 ± 8.5, and 33.2% of patients achieved a PASI75 response after MTX treatment. Patients carrying the ATP-binding cassette subfamily B member 1 gene (ABCB1) rs1045642 TT genotype were associated with more severe psoriasis skin lesion (P = 0.032). Furthermore, the ABCB1 rs1045642 TT genotype was found to be more frequent in non-responders (P = 0.017), especially in moderate-to-severe patients (P = 0.002) and patients without psoriatic arthritis (P = 0.026) after MTX treatment. CONCLUSION: We have demonstrated for the first time that polymorphism of the ABCB1 rs1045642 TT genotype is predictive of a worse clinical response of skin lesions to MTX therapy in a Chinese psoriatic population.

Smart identification of psoriasis by images using convolutional neural networks: a case study in China.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, which holds a high incidence in China. However, professional dermatologists who can diagnose psoriasis early and correctly are insufficient in China, especially in the rural areas. A smart approach to identify psoriasis by pictures would be highly adaptable countrywide and could play a useful role in early diagnosis and regular treatment of psoriasis. OBJECTIVES: Design and evaluation of a smart psoriasis identification system based on clinical images (without relying on a dermatoscope) that works effectively similar to a dermatologist. METHODS: A set of deep learning models using convolutional neural networks (CNNs) was explored and compared in the system for automatic identification of psoriasis. The work was carried out on a standardized dermatological dataset with 8021 clinical images of 9 common disorders including psoriasis along with full electronic medical records of patients built over the last 9 years in China. A two-stage deep neural network was designed and developed to identify psoriasis. In the first stage, a multilabel classifier was trained to learn the visual patterns for each individual skin disease. In the second stage, the output of the first stage was utilized to distinguish psoriasis from other skin diseases. RESULTS: The area under the curve (AUC) of the two-stage model reached 0.981 ± 0.015, which outperforms a single-stage model. And, the classifier showed superior performance (missed diagnosis rate: 0.03, misdiagnosis rate: 0.04) than 25 Chinese dermatologists (missed diagnosis rate: 0.19, misdiagnosis rate: 0.10) in the diagnosis of psoriasis on 100 clinical images. CONCLUSIONS: Using clinical images to identify psoriasis is feasible and effective based on CNNs, which also builds a solid technical base for smart care of skin diseases especially psoriasis using mobile/tablet applications for teledermatology in China.

[Analysis on operational safety of chronic radiation intestinal injury].

Objective: To investigate the safety and efficacy of surgical treatment for chronic radiation intestinal injury. Methods: A descriptive cohort study was performed. Clinical data of 73 patients with definite radiation history and diagnosed clinically as chronic radiation intestinal injury, undergoing operation at Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University from January 1, 2012 to February 28, 2019, were reviewed and analyzed retrospectively. Patients did not undergo operation or only received adhesiolysis were excluded. All the patients had preoperative examination and overall evaluation of the disease. According to severity of intestinal obstruction and patients' diet, corresponding nutritional support and conservative treatment were given. Surgical methods: The one-stage bowel resection and anastomosis was the first choice for surgical treatment of chronic radiation intestinal injury. Patients with poor nutritional condition were given enterostomy and postoperative enteral nutrition and second-stage stoma closure and intestinal anastomosis if nutritional condition improved. For those who were unable to perform stoma closure, a permanent stoma should be performed. Patients with severe abdominal adhesion which was difficult to separate, enterostomy or bypass surgery after adhesiolysis would be the surgical choice. For patients with tumor metastasis or recurrence, enterostomy or bypass surgery should be selected. Observation parameters: the overall and major (Clavien-Dindo grades III to V) postoperative complication within 30 days after surgery or during hospitalization; mortality within postoperative 30 days; postoperative hospital stay; time to postoperative recovery of enteral nutrition; time to removal of drainage tube. Results: Of the 73 patients who had been enrolled in this study, 10 were male and 63 were female with median age of 54 (range, 34-80) years. Preoperative evaluation showed that 61 patients had intestinal stenosis, 63 had intestinal obstruction, 11 had intestinal perforation, 20 had intestinal fistula, 3 had intestinal bleeding, and 6 had abdominal abscess, of whom 64(87.7%) patients had multiple complications. Tumor recurrence or metastasis was found in 15 patients. A total of 65(89.0%) patients received preoperative nutritional support, of whom 35 received total parenteral nutrition and 30 received partial parenteral nutrition. The median preoperative nutritional support duration was 8.5 (range, 6.0-16.2) days. The rate of one-stage intestine resection was 69.9% (51/73), and one-stage enterostomy was 23.3% (17/73). In the 51 patients undergoing bowel resection, the average length of resected bowel was (50.3±49.1) cm. Among the 45 patients with intestinal anastomosis, 4 underwent manual anastomosis and 41 underwent stapled anastomosis; 36 underwent side-to-side anastomosis, 5 underwent end-to-side anastomosis, and 4 underwent end-to-end anastomosis. Eighty postoperative complications occurred in 39 patients and the overall postoperative complication rate was 53.4% (39/73), including 39 moderate to severe complications (Clavien-Dindo grade III-V) in 20 patients (27.4%, 20/73) and postoperative anastomotic leakage in 2 patients (2.7%, 2/73). The mortality within postoperative 30 days was 2.7% (2/73); both patients died of abdominal infection, septic shock, and multiple organ failure caused by anastomotic leakage. The median postoperative hospital stay was 13 (11, 23) days, the postoperative enteral nutrition time was (7.2±6.9) days and the postoperative drainage tube removal time was (6.3±4.2) days. Conclusions: Surgical treatment, especially one-stage anastomosis, is safe and feasible for chronic radiation intestine injury. Defining the extent of bowel resection, rational selection of the anatomic position of the anastomosis and perioperative nutritional support treatment are the key to reduce postoperative complications.

Association of meteorological factors with seasonal activity of influenza A subtypes and B lineages in subtropical western China.

The seasonality of individual influenza subtypes/lineages and the association of influenza epidemics with meteorological factors in the tropics/subtropics have not been well understood. The impact of the 2009 H1N1 pandemic on the prevalence of seasonal influenza virus remains to be explored. Using wavelet analysis, the periodicities of A/H3N2, seasonal A/H1N1, A/H1N1pdm09, Victoria and Yamagata were identified, respectively, in Panzhihua during 2006-2015. As a subtropical city in southwestern China, Panzhihua is the first industrial city in the upper reaches of the Yangtze River. The relationship between influenza epidemics and local climatic variables was examined based on regression models. The temporal distribution of influenza subtypes/lineages during the pre-pandemic (2006-2009), pandemic (2009) and post-pandemic (2010-2015) years was described and compared. A total of 6892 respiratory specimens were collected and 737 influenza viruses were isolated. A/H3N2 showed an annual cycle with a peak in summer-autumn, while A/H1N1pdm09, Victoria and Yamagata exhibited an annual cycle with a peak in winter-spring. Regression analyses demonstrated that relative humidity was positively associated with A/H3N2 activity while negatively associated with Victoria activity. Higher prevalence of A/H1N1pdm09 and Yamagata was driven by lower absolute humidity. The role of weather conditions in regulating influenza epidemics could be complicated since the diverse viral transmission modes and mechanism. Differences in seasonality and different associations with meteorological factors by influenza subtypes/lineages should be considered in epidemiological studies in the tropics/subtropics. The development of subtype- and lineage-specific prevention and control measures is of significant importance.

LncRNA ZNF667-AS1 inhibits inflammatory response and promotes recovery of spinal cord injury via suppressing JAK-STAT pathway.

OBJECTIVE: The aim of this study was to explore the role of lncRNA ZNF667-AS1 in the recovery of spinal cord injury (SCI), and to investigate its underlying mechanism. MATERIALS AND METHODS: Mice were randomly assigned to the SCI group, the sham group and the lncRNA ZNF667-AS1 group, with 10 mice in each group. With Infinite Horizon device at a dose of 80 Kdyn, mice in the SCI group and the lncRNA ZNF667-AS1 group experienced SCI by an acute hit on the C5 spinous process. Before animal procedures, mice in the lncRNA ZNF667-AS1 group were additionally injected with overexpression lentivirus of lncRNA ZNF667-AS1. On the contrary, mice in the sham group only received laminectomy. After successful construction of the SCI model in mice, grip strength was accessed. LncRNA ZNF667-AS1 expression in spinal cord tissues before and after SCI was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), respectively. Meanwhile, the protein expression levels of relative genes in Janus Kinase-signal transducer and activator of transcription (JAK-STAT) pathway were detected by Western blot. RESULTS: Grip strength of forelimb in the SCI group recovered significantly slower than that of the sham group. With the prolongation of SCI, the expression of lncRNA ZNF667-AS1 was gradually decreased. However, the expression levels of JAK2, STAT3 and iNOS were upregulated in a time-dependent manner. In addition, mice in the lncRNA ZNF667-AS1 group presented remarkable grip strength recovery of forelimb after SCI. CONCLUSIONS: LncRNA ZNF667-AS expression is gradually downregulated after SCI. Meanwhile, it inhibits the inflammatory response and promotes SCI recovery via suppressing the JAK-STAT pathway.

Plasma HPV cell-free DNA monitoring in advanced HPV-associated oropharyngeal cancer.

Background: Measuring cell-free (cf)DNA in blood and tissues holds significant potential as a minimally invasive method for disease monitoring in cancer. Cancers arising in the oropharynx and causally linked to human papillomavirus (HPV) represent an ideal model in which to interrogate these methods. Patients and methods: We designed an ultrasensitive and quantitative droplet digital (dd)PCR assay to detect the five dominant high-risk HPV subtypes linked to oropharyngeal cancer (OPC). We enrolled a pilot observational cohort of 22 patients with advanced HPV+ OPC to evaluate the clinical utility of our assay and explore its predictive and prognostic potential. Results: Total tumor burden (TTB) strongly correlated with HPV cfDNA levels (R = 0.91, P = 2.3×10-6) at this cohort size, and in most cases more distant anatomic disease locations predicted increasing HPV cfDNA levels. All participants demonstrated a corresponding change in their HPV cfDNA levels at a median of 16 days (range 12-38) before restaging scans confirming treatment response or progression. Patients with locoregional disease in the head and neck or pulmonary-only metastases had worse outcomes (P = 0.01). Both TTB and median plasma HPV cfDNA levels negatively correlated with survival (R=-0.65, P = 0.01; R=-0.48, P = 0.05, respectively). Conclusion(s): Plasma HPV cfDNA monitoring recapitulates fluctuations in disease status. While blood-based HPV DNA monitoring does not currently have a role in managing HPV+ OPC, these data speak to their broad clinical potential in an era of precision medicine.

Plasma soluble cluster of differentiation 147 levels are increased in breast cancer patients and associated with lymph node metastasis and chemoresistance.

INTRODUCTION: Cluster of differentiation 147 (CD147) contributes to breast cancer invasion, metastasis, and multidrug resistance. Recent studies have shown that peripheral soluble CD147 (sCD147) is increased in hepatocellular tumour and multiple myeloma patients and correlated with disease severity. The primary aim of our study was to assess the level, as well as the biological and clinical significance of sCD147 in breast cancer. METHODS: We tested plasma sCD147 levels in 308 breast cancer patients by enzyme-linked immunosorbent assay between February 2014 and February 2017. A subset of 165 cases of benign breast diseases was included as a control group at the same period. We analysed the clinical significance of plasma sCD147 with relevance to clinicopathological factors of breast cancer patients. RESULTS: Plasma sCD147 levels were significantly higher in patients with primary breast cancer than those with benign breast diseases (P=0.001), in patients with locally advanced breast cancer (T3-T4 tumour) than those in early breast cancer (T1-T2 tumour; P=0.001), in patients with lymph node metastasis than in those without (P<0.001), and in patients with high recurrence risk than those with medium recurrence risk (P<0.001). Plasma sCD147 levels were also significantly higher in the chemotherapy-resistant group than in the chemotherapy-sensitive group (P=0.040). Plasma sCD147 was an independent predictor for lymph node metastasis in breast cancer patients (P=0.001). CONCLUSION: This is the first study to demonstrate that plasma sCD147 levels are elevated in breast cancer patients. Soluble CD147 is also associated with tumour size, lymph node metastasis, high recurrent risk, and chemoresistance. Our findings support that plasma sCD147 is an independent predictive factor for lymph node metastasis.

Amplicon-based next-generation sequencing of plasma cell-free DNA for detection of driver and resistance mutations in advanced non-small cell lung cancer.

Background: Genomic analysis of plasma cell-free DNA is transforming lung cancer care; however, available assays are limited by cost, turnaround time, and imperfect accuracy. Here, we study amplicon-based plasma next-generation sequencing (NGS), rather than hybrid-capture-based plasma NGS, hypothesizing this would allow sensitive detection and monitoring of driver and resistance mutations in advanced non-small cell lung cancer (NSCLC). Patients and methods: Plasma samples from patients with NSCLC and a known targetable genotype (EGFR, ALK/ROS1, and other rare genotypes) were collected while on therapy and analyzed blinded to tumor genotype. Plasma NGS was carried out using enhanced tagged amplicon sequencing of hotspots and coding regions from 36 genes, as well as intronic coverage for detection of ALK/ROS1 fusions. Diagnostic accuracy was compared with plasma droplet digital PCR (ddPCR) and tumor genotype. Results: A total of 168 specimens from 46 patients were studied. Matched plasma NGS and ddPCR across 120 variants from 80 samples revealed high concordance of allelic fraction (R2 = 0.95). Pretreatment, sensitivity of plasma NGS for the detection of EGFR driver mutations was 100% (30/30), compared with 87% for ddPCR (26/30). A full spectrum of rare driver oncogenic mutations could be detected including sensitive detection of ALK/ROS1 fusions (8/9 detected, 89%). Studying 25 patients positive for EGFR T790M that developed resistance to osimertinib, 15 resistance mechanisms could be detected including tertiary EGFR mutations (C797S, Q791P) and mutations or amplifications of non-EGFR genes, some of which could be detected pretreatment or months before progression. Conclusions: This blinded analysis demonstrates the ability of amplicon-based plasma NGS to detect a full range of targetable genotypes in NSCLC, including fusion genes, with high accuracy. The ability of plasma NGS to detect a range of preexisting and acquired resistance mechanisms highlights its potential value as an alternative to single mutation digital PCR-based plasma assays for personalizing treatment of TKI resistance in lung cancer.