[Antitumor effects of redox-responsive nanoparticles containing platinum（⠣）in ovarian cancer].

Objectives: To explore the antitumor effects of redox-responsive nanoparticles containing platinum(Ⅳ)-NP@Pt(Ⅳ) in ovarian cancer. Methods: Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(Ⅳ)-Pt(Ⅳ) can self-assemble into NP@Pt(Ⅳ). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(Ⅳ) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(Ⅳ) and NP@Pt(Ⅳ). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(Ⅳ) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(Ⅳ). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured. Results: The platinum release of NP@Pt(Ⅳ) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment (P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(Ⅳ) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(Ⅳ) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, P＜0.05). The half inhibitory concentrations of NP@Pt(Ⅳ) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 µmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 µmol/L) and cisplatin (5.21, 11.85, and 71.98 µmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(Ⅳ) was (33.91±3.80)%, which was significantly higher than that of Pt(Ⅳ) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, P＜0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(Ⅳ) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm3, which was significantly lower than those in control group [(1 349±161) mm3, P<0.001] and cisplatin group [(715±293) mm3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(Ⅳ) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(Ⅳ) compared with cisplatin. The change in body weight of mice in NP@Pt(Ⅳ) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining. Conclusion: Redox-responsive NP@Pt(Ⅳ), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.

[Statistical analysis of disability-adjusted life years for stomach and colorectal cancers in Changning District of Shanghai].

Objectives: To analyze the status and temporal changes of disability-adjusted life year (DALY) for stomach and colorectal cancers among registered permanent residents in Changning District of Shanghai Municipality, and provide scientific basis for the prevention and treatment of stomach and colorectal cancers in this district. Methods: Using the cancer registration data of stomach and colorectal cancers from 2002 to 2019, we estimated the indices such as the DALYs, the DALY crude rates, the age-standardized DALY rates, etc. Then we used the Joinpoint regression model to calculate the average annual percent change (AAPC) and annual percent change (APC) to explore the temporal variations in different periods. Results: The DALYs of stomach and colorectal cancers in Changning District from 2002 to 2019 were 55 931 person years and 65 252 person years, respectively. The crude rates of DALY were 512.16/105 and 597.51/105, respectively. We observed a higher disease burden in men than in women, and the peak rate of DALY in stomach cancer was in the 75-79 years age group, while in colorectal cancer the rate was in the 85-years-or-older age group. Joinpoint regression analysis showed that from 2002 to 2019, the age-standardized DALY rate of stomach cancer showed a downward trend (AAPC=-3.86%, P＜0.05), while the trend of colorectal cancer was not statistically significant(AAPC=-0.08%, P＞0.05). However, the trends in the age-standardized DALY rates of colorectal cancer were different between males and females, with males showing an upward trend (AAPC=1.24%, P＜0.05) and females showing a downward trend (AAPC=-1.67%, P＜0.05). Conclusions: The DALY of stomach and colorectal cancers in Changning District of Shanghai showed a decreasing trend. Males and the middle-aged and elderly populations are still the key targets for disease prevention and control in this district.

Postoperative pulmonary complications in older patients undergoing elective surgery with a supraglottic airway device or tracheal intubation.

The two most commonly used airway management techniques during general anaesthesia are supraglottic airway devices and tracheal tubes. In older patients undergoing elective non-cardiothoracic surgery under general anaesthesia with positive pressure ventilation, we hypothesised that a composite measure of in-hospital postoperative pulmonary complications would be less frequent when a supraglottic airway device was used compared with a tracheal tube. We studied patients aged ≥ 70 years in 17 clinical centres. Patients were allocated randomly to airway management with a supraglottic airway device or a tracheal tube. Between August 2016 and April 2020, 2900 patients were studied, of whom 2751 were included in the primary analysis (1387 with supraglottic airway device and 1364 with a tracheal tube). Pre-operatively, 2431 (88.4%) patients were estimated to have a postoperative pulmonary complication risk index of 1-2. Postoperative pulmonary complications, mostly coughing, occurred in 270 of 1387 patients (19.5%) allocated to a supraglottic airway device and 342 of 1364 patients (25.1%) assigned to a tracheal tube (absolute difference -5.6% (95%CI -8.7 to -2.5), risk ratio 0.78 (95%CI 0.67-0.89); p < 0.001). Among otherwise healthy older patients undergoing elective surgery under general anaesthesia with intra-operative positive pressure ventilation of their lungs, there were fewer postoperative pulmonary complications when the airway was managed with a supraglottic airway device compared with a tracheal tube.

[Analysis of prognosis and related factors in oldest-old patients with left-side or right-side colon cancer after hemicolectomy].

Objective: This study aimed to explore the difference of prognosis in oldest-old colon cancer patients between the left-side and right-side hemicolectomy. Methods: A total of 238 oldest-old (≥75 years old) colon cancer patients who received surgical treatment in Gastrointestinal Surgery Department of Beijing Hospital from December 2010 to December 2020 were retrospectively collected. They were divided into right-side hemicolectomy (RCC) group (130 cases) and left-side hemicolectomy (LCC) group (108 cases) by surgical methods. The difference in postoperative short-term complications and long-term prognosis was compared between the two groups, and the related factors of postoperative death was analyzed using multivariate Cox regression model. Results: The age of 238 oldest-old patients with colon cancer ranged from 75 to 93 years old (80.5±3.7). There were 128 males and 110 females. The ages of patients in the LCC group and RCC group were (80.4±3.7) and (80.6±3.7) years old (P=0.699), respectively. There was no significant difference in gender, body mass index (BMI) and co-existing chronic diseases between two groups (P>0.05). The proportion of the duration of surgery exceeding 170 min in the LCC group was significantly higher than that in the RCC group (56.5% vs 43.1%, P=0.039). The incidence of postoperative short-term complications in RCC group was slightly higher than LCC group (P>0.05), and there was no significant difference in overall survival (OS), tumor-specific survival (CSS) and disease-free survival (DFS) between two groups. However, the two groups had different prognostic risk factors, pathological Ⅳ stage (HR=28.970,95%CI:1.768-474.813,P=0.018), intraoperative bleeding (HR=2.297,95%CI:1.351-3.907,P=0.002) and cancer nodules (HR=2.044,95%CI:1.047-3.989,P=0.036) were independent prognostic risk factors in LCC group. Underweight (HR=0.428,95%CI:0.192-0.955,P=0.038), overweight(HR=0.316,95%CI:0.125-0.800,P=0.015),obesity (HR=0.211,95%CI:0.067-0.658,P=0.007), lymph node metastasis (HR=2.682,95%CI:1.497-4.807,P=0.001), tumor nodule (HR=2.507,95%CI:1.301-4.831,P=0.027) and postoperative length of stay of 9 days (HR=1.829,95%CI:1.070-3.128,P=0.006) were independent risk factors for poor prognosis in RCC group. Conclusions: The duration of surgery of oldest-old colon cancer patients in the LCC group was longer than that in the RCC group. However, there was no significant difference in the incidence of postoperative complications between the two groups. High pathological stage, more intraoperative bleeding and cancer nodules were independent prognostic risk factors in the LCC group. Abnormal BMI, lymph node metastasis, cancer nodules and postoperative length of stay were independent risk factors for poor prognosis in the RCC group.

Melanoma secretion of transforming growth factor-ß2 leads to loss of epidermal AMBRA1 threatening epidermal integrity and facilitating tumour ulceration.

BACKGROUND: For patients with early American Joint Committee on Cancer (AJCC)-stage melanoma the combined loss of the autophagy regulatory protein AMBRA1 and the terminal differentiation marker loricrin in the peritumoral epidermis is associated with a significantly increased risk of metastasis. OBJECTIVES: The aim of the present study was to evaluate the potential contribution of melanoma paracrine transforming growth factor (TGF)-ß signalling to the loss of AMBRA1 in the epidermis overlying the primary tumour and disruption of epidermal integrity. METHODS: Immunohistochemistry was used to analyse AMBRA1 and TGF-ß2 in a cohort of 109 AJCC all-stage melanomas, and TGF-ß2 and claudin-1 in a cohort of 30 or 42 AJCC stage I melanomas, respectively, with known AMBRA1 and loricrin (AMLo) expression. Evidence of pre-ulceration was analysed in a cohort of 42 melanomas, with TGF-ß2 signalling evaluated in primary keratinocytes. RESULTS: Increased tumoral TGF-ß2 was significantly associated with loss of peritumoral AMBRA1 (P < 0·05), ulceration (P < 0·001), AMLo high-risk status (P < 0·05) and metastasis (P < 0·01). TGF-ß2 treatment of keratinocytes resulted in downregulation of AMBRA1, loricrin and claudin-1, while knockdown of AMBRA1 was associated with decreased expression of claudin-1 and increased proliferation of keratinocytes (P < 0·05). Importantly, we show loss of AMBRA1 in the peritumoral epidermis was associated with decreased claudin-1 expression (P < 0·05), parakeratosis (P < 0·01) and cleft formation in the dermoepidermal junction (P < 0·05). CONCLUSIONS: Collectively, these data suggest a paracrine mechanism whereby TGF-ß2 causes loss of AMBRA1 overlying high-risk AJCC early-stage melanomas and reduced epidermal integrity, thereby facilitating erosion of the epidermis and tumour ulceration.

[Application values of right atrial volume, myocardial strain and strain rate in evaluating right atrial function in patients with essential hypertension with normal left ventricular ejection fraction].

Objective: To explore the application values of right atrial (RA) volume, myocardial strain and strain rate in evaluating right atrial functions in patients with essential hypertension (EHT) with normal left ventricular ejection fraction (LVEF). Methods: We retrospectively collected a total of 126 EHT patients with normal LVEF, including 66 males and 60 females, age from 18 to 83(48±15) years from the Affiliated Changzhou No.2 People's Hospital with Nanjing Medical University from March, 2018 to May, 2020. According to the left ventricular mass index, those patients were divided into without left ventricle hypertrophy (LVH) group (n=66) and LVH group (n=60), and 83 healthy volunteers were enrolled as control group, which including 42 males and 41 females, age from 14 to 88 (48±16) years. The total, passive and active RA emptying fraction (total RAEF, passive RAEF and active RAEF) were measured by using RA volumes method. The RA strain (S-reservoir, S-conduit, S-booster pump) and the strain rate (SR-reservoir, SR-conduit, SR-booster pump) were measured by two-dimensional speckle tracking echocardiography. Total RAEF, S-reservoir, and Sr-reservoir represented the reservoir function, while passive RAEF, S-conduit, and Sr-conduit represented the conduit function, and active RAEF, S-booster pump and Sr-booster pump represented the booster pump function, respectively. Than the values between the EHT patients and normal subjects, and the values among the EHT patients without LVH, EHT patients without LVH and normal subjects were compared. Results: The value of active RAEF was significantly lower in EHT patient than normal controls (40.1%±10.5% vs 45.4%±11.1%,P=0.001). There were significant differences among EHT patients without LVH, EHT patients with LVH and normal subjects in passive RAEF and active RAEF (passive RAEF: 40.2%±9.3% vs 36.4%±10.7% vs 36.5%±9.4%, P=0.038, active RAEF: 39.8%±10.6% vs 40.4%±10.4% vs 45.4%±11.1%, P=0.002). There were significant differences in S-reservoir, S-conduit, S-booster pump, SR-reservoir, SR-conduit and SR-booster pump between EHT patients and normal subjects [S-reservoir: 34.8%±13.7% vs 45.0%±13.3%, S-conduit: 18.3%±9.4% vs 26.5%±9.6%, S-booster pump: 16.4%±7.3% vs 18.6%±7.1%, SR-reservoir: (1.6±0.6)/s vs (2.0±0.6)/s, SR-conduit: (-1.2±0.5)/s vs (-1.6±0.6)/s, SR-booster pump: (-1.7±0.6)/s vs (-2.3±0.6)/s; all P<0.05]. The trend tests showed normal controls achieved the largest the absolute values of S-reservoir, S-conduit, SR-reservoir, SR-conduit, SR-booster pump, followed by EHT patients without LVH and EHT patients with LVH(all P<0.001). Conclusions: Using RA volume, myocardial strain and strain rate can detect the RA impaired reservoir, conduit, and the booster pump functions in EHT patients with normal LVEF, and the RA functions were damaged more significantly in EHT patients with LVH.

[Two-dimensional equivalent mechanical modeling and finite element analysis of normal female pelvic floor system].

Objective: To construct the geometric model of the pelvic floor by a two-dimensional equivalent mechanics method, and to explore the effect of the shape and position of pelvic floor organs and tissues on the biomechanical properties of the pelvic floor under different abdominal pressure. Methods: A 28-year-old healthy and symmetrical married infertile female volunteer was included. The pelvic floor tissue was scanned in the supine position using a 3.0T magnetic resonance scanner (Philips Company, Holland). Based on the method of magnetic resonance imaging (MRI) two-dimensional parameter measurement and computer aided design, the geometric model and finite element model of the female pelvic floor were established, and the biomechanical characteristics of the pelvic floor support system under different abdominal pressure were analyzed. Results: In this study, four different working conditions of the pelvic floor force were simulated under 60, 99, 168, and 208 cmH2O (1 cmH2O=0.098 kPa) abdominal pressure loads. The trend was as follows: under the abdominal pressure load, the retrograde flexion of the uterus occurred, the cervical, the middle and upper vaginal segment and the levator anus muscle had the characteristic change of mechanical axial direction pointing to the sacrum and coccyx, and the deformation of the levator anus muscle in the horizontal direction was greater than that in the vertical direction. With the increase of the abdominal pressure, the maximum stress values of the pelvic floor whole system of healthy subjects under four different working conditions were 0.194 3, 0.389 6, 0.557 1, and 0.627 5 MPa, respectively, and the maximum displacement values were 10, 14, 21 and 25 mm, respectively. The maximum stress values of the cervical and vaginal middle and upper segment were 0.111 7, 0.161 8, 0.250 6, and 0.304 1 MPa, respectively, and the maximum displacement values were 3, 6, 9, and 11 mm, respectively. The maximum stress of the perineal body was 0.063 4, 0.119 6, 0.235 2, and 0.288 0 MPa, and the maximum displacement was 1, 2, 4, and 5 mm. The maximum stress values of the levator anus muscle were 0.194 3, 0.389 6, 0.557 1, and 0.627 5 MPa, and the maximum displacement values were 2, 4, 7, and 8 mm, respectively. The maximum stress and maximum displacement of pelvic organs increased with the increase of the abdominal pressure under different working conditions. The stress axial relationship of normal female pelvic floor was that the middle and upper segment of uterus and vagina mainly acted on the sacrococcyx and the levator anus muscle, and the lower vaginal segment acts on the perineal body. Conclusions: The two-dimensional equivalent mechanical modeling and finite element analysis of the female pelvic floor system can accurately reflect the biomechanical characteristics of the female pelvic floor, and the resultant stress direction of the pelvic organs points to the sacrum and coccyx. The sacrum and coccyx, levator anus and perineal body play important stress supporting roles in the pelvic floor system.

[Analysis on prevalence and epidemic risk of animal plague in different ecological plague foci in Inner Mongolia Autonomous Region].

The risk of plague epidemics and relapse of various types of plague foci persists in Inner Mongolia Autonomous Region. For Marmota sibirica plague foci, the animal plague has not been found but antibody has been detected positive. Nowadays, Marmota sibirica has been increasing in population and distribution in China. In bordering countries Mongolia and Russia, the animal plague has been continuously prevalent. For Spermophilus dauricus plague foci, the animal plague has been taken place now and then. Compared to the above foci, the animal plague is most prevalent in Meriones unguiculatus plague foci and frequently spread to humans. Due to higher strain virulence and historical disaster in Marmota sibirica plague foci and Spermophilus dauricus plague foci, plague prevention and control should be strengthened on these foci. In addition to routine surveillance, epidemic dynamics need to be further monitored in these two foci, in order to prevent their relapse and spread to humans.

[Analysis of pathogenic bacteria in cirrhotic patients complicated with bacterial infection in a tertiary hospital in Xinjiang].

Objective: To understand the species, distribution, and extent of drug resistance of pathogenic bacteria in patients with liver cirrhosis combined with bacterial infection in a tertiary hospital in Xinjiang. Methods: 1 271 cases with liver cirrhosis combined with infection were analyzed retrospectively for pathogenic bacterial species and drug resistance condition in different bacterial strain. Results: Among the 1 271 cases with liver cirrhosis, 480 were combined with infection, and the infection rate was 37.8%. The majority of infected patients had decompensated cirrhosis (438 cases). Peritoneum (327 cases, 60.8%) was the common infection site, followed by lungs (16.9%). 343 strains of pathogens were isolated from 480 infected cases, of which 289 strains were among the top 10 common distinct bacteria, accounting for 76.5% and 23.5% of Gram-negative and positive bacteria. The first top three strains were Escherichia coli. (33.2%), Klebsiella pneumoniae (11.4%), and Enterococcus faecium (11.1%), and there were differences in the drug resistance rates of each strain. Conclusion: In a tertiary hospital in Xinjiang, patients with decompensated cirrhosis have a high rate of bacterial infection. The pathogenic bacteria are diverse, mainly Gram-negative bacteria; however, the infection rate of Gram-positive bacteria such as Enterococcus is gradually increasing. Additionally, according to the bacterial properties, they are divided into four categories: Enterobacter, Enterococcus, glucose non-fermenting bacteria and Staphylococcus, and it is found that even the same species of bacteria have different drug resistance rates.

[The analysis of long-term prognostic factors after laparoscopic liver resection for intrahepatic cholangiocarcinoma and establishment of survival Nomogram model].

Objective: To establish a survival prediction model based on the independent prognostic factors of long-term prognosis after laparoscopic liver resection(LLR) for intrahepatic cholangiocarcinoma(ICC). Methods: The clinical and pathological data of 351 consecutive patients with ICC who received radical LLR in 13 Chinese medical centers from August 2010 to May 2021 were collected retrospectively. There were 190 males and 161 females,aged(M(IQR)) 61(14)years(range:23 to 93 years). The total cohort was randomly divided into a training dataset(264 cases) and a validation dataset(87 cases). The patients were followed up by outpatient service or telephone,and the deadline for follow-up was October 2021. Based on the training dataset,the multivariate Cox proportional hazards regression model was used to screen the independent influencing factors of long-term prognosis to construct a Nomogram model. The Nomogram model's discrimination,calibration,and clinical benefit were evaluated through internal and external validation,and an assessment of the overall value of two groups was made through the use of a receiver operating characteristic(ROC) curve. Results: There was no significant difference in clinical and pathological characteristics and long-term survival results between the training and validation datasets(all P>0.05). The multivariate Cox analysis showed that CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis were independent prognostic factors for ICC patients after LLR(all P<0.05). The survival Nomogram was established based on the independent prognostic factors obtained from the above screening. The ROC curve showed that the area under the curve of 1, 3 and 5-year overall survival rates of patients in the training dataset were 0.794(95%CI:0.721 to 0.867),0.728(95%CI:0.618 to 0.839) and 0.799(95%CI:0.670 to 0.928),and those in the validation dataset were 0.787(95%CI:0.660 to 0.915),0.831(95%CI:0.678 to 0.983) and 0.810(95%CI:0.639 to 0.982). Internal and external validation proved that the model exhibited a certain discrimination,calibration,and clinical applicability. Conclusion: The survival Nomogram model based on the independent influencing factors of long-term prognosis after LLR for ICC(including CA19-9,CA125,conversion to laparotomy during laparoscopic surgery,and lymph node metastasis) exhibites a certain differentiation,calibration,and clinical practicability.

[Association between cord blood BPDE-DNA and neurodevelopment of children aged 0 and 2 years: A birth cohort study].

Objective: To explore the effects of mothers' exposure to polycyclic aromatic hydrocarbons during pregnancy on their children's neurobehavioral development. Methods: In November 2009 to April 2010, a total of 221 pairs of mother-newborn pairs were recruited from two cooperative hospitals in Taiyuan, and their children were followed up at age two. High performance liquid chromatography was used to determine the level of BPDE-DNA in cord blood leukocytes. The Neonatal behavioral neurological assessment (NBNA) was used to assess the neurodevelopment of newborns, and the Gesell Development Scale was used to measure neurodevelopmental indexes of 2-year-old children. NBNA includes behavior, active and passive tone, primitive reflexes and general assessment, with a total score of 40 points. The Gesell Developmental Schedules consisted of four sub-scales: motor development, adaptive behavior development, language development and personal-social behavior development. We used mean and standard deviation to describe continuous variables with normal distribution, median (interquartile range) to describe continuous variables with skewed distribution, and frequency and proportion to describe categorical variables. Restricted cubic spline models were applied to assess the dose-response relationships between maternal prenatal polycyclic aromatic hydrocarbons exposure and children's neurobehavioral development at two years old. Generalized linear models were applied to evaluate the effect of exposure to maternal prenatal polycyclic aromatic hydrocarbons exposure on children's neurobehavioral development at 0 and two years old. Results: The NBNA score was 38.0±0.8, and the scores of 2-year-old children's motor, adaptive, language and personal-social were 111.6±15.0, 110.5±14.6, 108.8±17.2 and 111.7±14.5, respectively. After adjusting for confounding factors, there is no dose-response association between the cord blood BPDE of pregnant women and neonatal NBNA scores, but there were dose-response associations between BPDE and scores of 2-year-old children's motor, adaptive, language and personal-social. A unit increase in cord blood ln (BPDE-DNA), the score of motor, adaptive, language and personal-social of 2-year-old children decreased on average by 4.54、6.29、8.41 and 7.02 points. Conclusion: Maternal exposure to polycyclic aromatic hydrocarbons during pregnancy is associated with decreased children's neurobehavioral development at two years old.

Collision between soliton and polarization domain walls in fiber lasers.

We report on the experimental observation of coexistence of solitons and polarization domains, as well as features of soliton collision with polarization domain walls (or kink solitons) in a single mode fiber laser. Depending on the sign of cavity dispersion, either bright or dark solitons have been formed in our fiber laser. Under suitable laser operation conditions, they could even coexist with polarization domains and collide with the domain walls. We show experimental evidence of both the elastic and inelastic soliton collisions with the domain wall solitons. Some interesting features of soliton interaction with polarization domains in a fiber laser are also firstly revealed.

Dark-bright soliton trapping in a fiber laser.

We report, to the best of our knowledge, the first experimental observation of coexistence of scalar dark and bright solitons in a fiber laser operating in the near zero-dispersion regime. We show that because of the incoherent cross coupling, under suitable conditions a bright soliton formed in the net anomalous cavity dispersion regime could bind with a dark soliton formed in the net normal cavity dispersion regime in a fiber laser. The properties of the dark and bright solitons, as well as their bound states, are experimentally investigated. The numerical simulations based on the coupled Ginzburg-Landau equations have reproduced the experimental results well.

Coherently coupled vector black solitons in a quasi-isotropic cavity fiber laser.

We report the first experimental observation of coherently coupled black-black solitons in a quasi-isotropic cavity fiber laser with normal cavity dispersion. The properties of the vector solitons accord well with the theoretical predictions based on the coherently coupled nonlinear Schrödinger equations. Numerical studies and experimental results clearly confirmed the existence of the highly robust vector black solitons in the fiber laser system.

Epidermal autophagy and beclin 1 regulator 1 and loricrin: a paradigm shift in the prognostication and stratification of the American Joint Committee on Cancer stage I melanomas.

BACKGROUND: The updated American Joint Committee on Cancer (AJCC) staging criteria for melanoma remain unable to identify high-risk stage I tumour subsets. OBJECTIVES: To determine the utility of epidermal autophagy and beclin 1 regulator 1 (AMBRA1)/loricrin (AMLo) expression as a prognostic biomarker for AJCC stage I cutaneous melanoma. METHODS: Peritumoral AMBRA1 expression was evaluated in a retrospective discovery cohort of 76 AJCC stage I melanomas. AMLo expression was correlated with clinical outcomes up to 12 years in two independent powered, retrospective validation and qualification cohorts comprising 379 AJCC stage I melanomas. RESULTS: Decreased AMBRA1 expression in the epidermis overlying primary melanomas in a discovery cohort of 76 AJCC stage I tumours was associated with a 7-year disease-free survival (DFS) rate of 81·5% vs. 100% survival with maintained AMBRA1 (P < 0·081). Following an immunohistochemistry protocol for semi-quantitative analysis of AMLo, analysis was undertaken in validation (n = 218) and qualification cohorts (n = 161) of AJCC stage I melanomas. Combined cohort analysis revealed a DFS rate of 98·3% in the AMLo low-risk group (n = 239) vs. 85·4% in the AMLo high-risk cohort (n = 140; P < 0·001). Subcohort multivariate analysis revealed that an AMLo hazard ratio (HR) of 4·04 [95% confidence interval (CI) 1·69-9·66; P = 0·002] is a stronger predictor of DFS than Breslow depth (HR 2·97, 95% CI 0·93-9·56; P = 0·068) in stage IB patients. CONCLUSIONS: Loss of AMLo expression in the epidermis overlying primary AJCC stage I melanomas identifies high-risk tumour subsets independently of Breslow depth. What's already known about this topic? There is an unmet clinical need for biomarkers of early-stage melanoma. Autophagy and beclin 1 regulator 1 (AMBRA1) is a proautophagy regulatory protein with known roles in cell proliferation and differentiation, and is a known tumour suppressor. Loricrin is a marker of epidermal terminal differentiation. What does this study add? AMBRA1 has a functional role in keratinocyte/epidermal proliferation and differentiation. The combined decrease/loss of peritumoral AMBRA1 and loricrin is associated with a significantly increased risk of metastatic spread in American Joint Committee on Cancer (AJCC) stage I tumours vs. melanomas, in which peritumoral AMBRA1 and loricrin are maintained, independently of Breslow depth. What is the translational message? The integration of peritumoral epidermal AMBRA1/loricrin biomarker expression into melanoma care guidelines will facilitate more accurate, personalized risk stratification for patients with AJCC stage I melanomas, thereby facilitating stratification for appropriate follow-up and informing postdiagnostic investigations, including sentinel lymph node biopsy, ultimately resulting in improved disease outcomes and rationalization of healthcare costs.

Reconstruction and analysis of the aberrant lncRNA-miRNA-mRNA network in systemic lupus erythematosus.

OBJECTIVE: A new perspective of determining the pathophysiology of systemic lupus erythematosus (SLE) development is required. The current study explores the aberrant expression of long non-coding RNAs (lncRNA), microRNA (miRNA) and mRNA. The study further constructs and analyses the lncRNA-miRNA-mRNA network to elucidate their gene regulation roles in SLE. METHOD: We extracted mRNA, lncRNA and miRNA from the whole venous blood of 20 SLE patients and 20 normal control (NC) healthy individuals. A lncRNA-mRNA-miRNA network in SLE was constructed using a bioinformatics approach. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using the Cytoscape plug-in BinGo, the DAVID database and Cytoscape software to explore the function of mRNAs in this network. RESULT: A total of 855 mRNA, 7311 lncRNA and 134 miRNA with differentially expressed profiles were identified. Meanwhile, we established a competing endogenous RNA (ceRNA) subnetwork composed of 52 differentially expressed lncRNAs (DElncRNAs), seven differentially expressed miRNAs and 10 differentially expressed mRNAs. We extracted the subnetwork from the ceRNA network and found that three novel miRNAs were key: hsa-miR-145, hsa-miR-17 and hsa-miR-143. We also deduced that the DElncRNAs MIAT and NEAT1 might play crucial roles in the pathogenesis of SLE. The results were verified by bioinformatics analysis. CONCLUSION: Our results provide a novel perspective for studying lncRNA-related and miRNA-related ceRNA networks in SLE.

Adaptation strategies of Pseudomonas protegens SN15-2 to hyperosmotic growth environment.

AIMS: This study investigated the adaptation strategies of Pseudomonas protegens to hyperosmotic growth environments (HGE). METHODS AND RESULTS: The current study combined transcriptomics and proteomics to provide an overview of the molecular mechanism of P. protegens adaptation to HGE. The results revealed that HGE exerted prominent impact on the synthesis of proteins involved in multiple cellular functions. Comparison of the differentially accumulated proteins at both transcriptomics and proteomics levels indicated the existence of complex post-transcriptional modification during P. protegens hyperosmotic adaptation. CONCLUSIONS: During HGE adaptation, the cells form a complex self-protection mechanism. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of the current study can help researchers to gain insights regarding the mechanism of P. protegens adaptation to HGE. These findings provide information for the application of stress methods and facilitate its broad commercial utilization.

PCNA and GSK3ß interact with each other to regulate H1299 lung adenocarcinoma cells apoptosis.

Glycogen synthase kinase beta (GSK3ß) is considered as a promising target for lung cancer treatment and its inhibitor lithium chloride (LiCl) is widely regarded as having potent anti-proliferative and apoptosis-modulating activities. Proliferating cell nuclear antigen (PCNA), as an auxiliary protein for DNA polymerase delta, which regulates DNA replication and repair, has been reported to play an important role in regulating apoptosis. Here, we showed that GSK3ß interacted with PCNA in H1299 lung adenocarcinoma cells using GST pull-down and co-immunoprecipitation experiments. We discovered that their interaction can be enhanced within the first 3 h after UVC irradiation and decreased gradually with time. Overexpression of PCNA protein decreased GSK3ß Ser9 phosphorylation, whereas knockdown of PCNA using small interfering RNA (siRNA) increased Ser9 phosphorylated GSK3ß, which was attenuated by phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 after UVC irradiation, indicating the involvement of the PI3K-AKT pathway. Functional analyses suggested that downregulation of PCNA sensitized H1299 cells to LiCl-induced apoptosis. Thus, our results unraveled a novel regulatory of GSK3ß by PCNA and provided a promising direction for treatment of lung cancer.

[Study on the effect of simple incision of ventral tunica albuginea on the correction of penile curvature in hypospadias].

Objective: To investigate the therapeutic effect of simple tunica albugineaincision and ventral penile lengthening surgery on the correction of penile curvature due to asymmetry of the cavernous bodies in hypospadias. Methods: A retrospective analysis was performed in 39 children with hypospadias who underwent simple tunica albuginea incision and ventral penile lengthening surgery for correcting asymmetry of the cavernous bodies from January 2016 to December 2018(36 of them were from Department of Pediatric Urology surgery, The Children's Hospital, Zhejiang University School of Medicine, and 3 from Department of Urology surgery, Affiliated Hospital ofJiaxing University), all of whom aged from 0.5 to 5, with a median age of 1.1 years. During the first stage of the operation, firstly penile skin and sarcoma was released by completely degloving the skin and fascia of penis, secondly the factor of short urethral plate was solved by transection of urethral plate, and then the dorsal length of penis (A), the ventral length of the penis before and after straightening by incision of tunica albuginea (B and C) were measured and recorded; onto the second stage of the operation, an artificial erection test was performed to observe the curvature of the penis, the dorsal and ventral length of the penis (D and E) were measured. The dorsal and ventral length of the penis before and after straightening were compared. Results: The dorsal length of penis (A) was 33-39(35.6±3.2) mm, the length of ventral length of penis before straightening (B) was 28-35 (29.8±2.8) mm and the length of ventral length of penis after straightening (C) was 32-38 (34.3±2.1) mm, which were measured during the first stage of operation, and the difference between B and C was statistically significant (P<0.05), while the difference between A and C was not statistically significant (P>0.05). The dorsal length of penis (D) was34-41 (36.4±2.5) mm and the ventral length of penis (E) was 33-40 (35.7±3.6) mm, which were measured during the second stage of operation, and there was no significant difference between D and E (P>0.05). The degree of penile curvature at the time of erection was less than 15° by measuring with the side photos in all patients during 0.5 to 2.5 years of follow-ups with an average of 1.7 years. Conclusions: Penile curvature due to the asymmetry of the cavernous bodies could be effectively corrected by simple incision of ventral tunica albuginea, which showed a good result of early follow-up. The effect of this surgery on ventral penile straightening could be verified by measuring and comparing the ventral and dorsal length of penis during surgery.

IDENTIFICATION OF A NOVEL MUTATION IN THE MMAA GENE IN A CHINESE BOY WITH ISOLATED METHYLMALONIC ACIDEMIA.

BACKGROUND: Isolated methylmalonic acidemia refers to a group of inborn errors of metabolism characterized by elevated methylmalonic acid concentrations in the blood and urine. It occurs in approximately one to three out of every 100 thousand Chinese newborns. Mutations in the MMAA gene cause isolated methylmalonic acidemia. CASE PRESENTATION: A 13-month-old boy was diagnosed with isolated methylmalonic acidemia. We identified two mutations in the MMAA gene in this case: c.491G>A and c.650T>A. The c.491G>A is a novel mutation in the MMAA gene. The boy is a heterozygous carrier of both mutations. The boy was treated with intravenous sodium benzoate and fluids. His sensorium gradually improved and he recovered from the acute illness. Other family members are heterozygous carriers of either mutations but with no symptoms. CONCLUSIONS: We identified a novel c.491G>A mutation in the MMAA gene. Heterozygous carriers of both c.491G>A and c.650T>A mutations are associated with isolated methylmalonic acidemia.