Gut microbiota, a potential cause of higher insulin sensitivity in children with Prader-Willi syndrome.

PURPOSE: Obesity is the main driving factor for comorbidities in Prader-Willi syndrome (PWS) patients due to overeating behaviors. The gut microbiota has been implicated in the etiology of obesity and associated comorbidities. The purpose of the present study was to characterize the fecal microbiota in Chinese patients with PWS and compare it to that of patients with obesity as well as healthy controls. METHODS: We conducted a cross-sectional study with 35 PWS patients (PWS), 35 patients with obesity (OB), and 35 healthy controls (HC). Metagenomic sequencing was performed in stool samples. RESULTS: The composition of the fecal microbiota in PWS patients differed from that of participants in the OB and HC groups. It was characterized by increased Akkermansia Eubacterium, Eubacterium rectale, and Roseburia intestinalis and decreased Parabacteroides and Phascolarctobacterium. Additionally, the homeostatic model assessment of insulin resistance (HOMA-IR) was lower in PWS patients than in patients with obesity. Spearman rank correlation analysis showed that Achromobacter, Acidiphilium, Xylophilus, and Frisingicoccus were significantly negatively correlated with HOMA-IR. CONCLUSION: The composition of the gut microbiota in Chinese PWS patients differed from that in patients with obesity, which might contribute to higher insulin sensitivity in PWS patients.

[A nomogram prediction model for individualized prediction of the risk of covert (minimal) hepatic encephalopathy occurrence in patients with liver cirrhosis].

Objective: To construct an individualized nomogram prediction model for predicting the risk of the occurrence of covert hepatic encephalopathy (CHE) in patients with liver cirrhosis. Methods: 325 cases of liver cirrhosis admitted from January 2020 to December 2022 were selected as the study subjects. Patients were divided into training (n=213) and validation (n=112) sets using a cluster randomization method. The risk factors for CHE occurrence in patients with cirrhosis in the training set were analyzed by univariate and multivariate logistic regression. A prediction model related to the nomogram was established. Results: Independent risk factors for the occurrence of CHE in patients with cirrhosis were a history of hepatic encephalopathy, co-infection, gastrointestinal bleeding, severe ascites, prothrombin time ≥16 seconds, high total bilirubin, and high blood ammonia levels (P<0.05). Nomogram model validation results: The model had a net benefit for the training and validation sets, with C-indices of 0.830 (95%CI: 0.802-0.858) and 0.807 (95%CI: 0.877-0.837), respectively, within the range of 0-96%. The calibration curves of both sets were evenly close to the ideal curves. The AUCs for the ROC curves in both sets were 0.827 (95%CI: 0.796-0.858) and 0.811 (95%CI: 0.787-0.836), respectively. Conclusion: Patients with cirrhosis have many risk factors for CHE occurrence. The nomogram model constructed based on these risk factors possesses a good predictive value for assessing CHE occurrence in cirrhotic patients.

[Quantitative study of supraspinatus tendon injury grading based on synthetic magnetic resonance imaging].

Objective: To investigate the diagnostic value of quantitative parameters of synthetic magnetic resonance imaging (SyMRI) in the grade of supraspinatus tendon injury. Methods: Ninety-seven patients with clinical definite of supraspinatus tendon injury from July 2021 to July 2022 in General Hospital of Ningxia Medical University were prospectively collected (case group), including 54 males and 43 females, with an age of 29 to 56 (37.4±9.6) years. According to the results of shoulder arthroscopy, the case group were divided into three subgroups included tendinopathy group (37 cases, grade Ⅱ), partial tear group (34 cases, grade Ⅲ) and complete tear group (26 cases, grade Ⅳ). During the same period, 28 normal rotator cuff volunteers without supraspinatus tendon injury were recruited (control group), including 16 males and 12 females, aged 23 to 49 (36.1±7.2) years, and marked as grade Ⅰ. All the subjects underwent MRI scan of articulatio humeri included T1-weighted imaging(T1WI) fast spin echo(FSE) sequences in axial view, T2-weighted imaging(T2WI) fat suppression(FS) sequences in axial view, T2WI FS sequences in oblique coronal view, proton density-weighted (PDW) imaging in oblique sagittal view and SyMRI in oblique coronal view. The supraspinatus tendon was divided into lateral, medial and middle subregions according to its shape in oblique coronal T2WI view, two radiologists measured the T1, T2 and PD values of the supraspinatus tendon. The interclass correlation coefficient (ICC) were used to compare the consistency between and within observers. One-way analysis of variance or Kruskal-Wallis H test were used to compare the differences of quantitative parameters in different grades, the multivariate logistic regression model was used to analyze the risk factors of supraspinatus tendon injury grade, and the receiver operating characteristic (ROC) curves and area under curve (AUC) was drawn and calculated to evaluate the diagnostic efficacy. The Spearman correlation was used to analyze the correlation between the quantitative values and grades of supraspinatus tendon injury. Results: The ICC values of T1, T2 and PD values for the three subregions of the supraspinatus tendon were greater than 0. 700. The differences of T1 values in the lateral subregion, T2 values in the lateral and middle subregions were statistically significant in the overall comparison across different grades (all P<0. 001).The differences of T1 values in the middle and medial subregions, T2 values in the medial subregion and PD values in the lateral, middle and medial subregions were not statistically significant in the overall comparison of different grades (all P>0. 05). Multiple logistic regression model analysis showed that T2 values in the lateral and middle subregions were related factors for the grade of supraspinatus tendon injury[ OR (95%CI):1.123 (1.037-1.216), 0.122 (1.151-1.197);all P<0.001 ]. The AUC of the T2 values in lateral subregion diagnosing grade Ⅰ vs grade Ⅳ, grade Ⅱ vs grade Ⅳ and grade Ⅲ vs grade Ⅳ were 0.891(95%CI: 0.801-0.981), 0.797(95%CI: 0.680-0.914), 0.723(95%CI: 0.594-0.853) (all P<0.001), and the AUC of the T2 values in middle subregion diagnosing grade Ⅰ vs Ⅳ, grade Ⅱ vs Ⅳ, grade Ⅱ vs Ⅲ, and grade Ⅰ vs Ⅲ were 0.946 (95%CI: 0.849-0.989), 0.886 (95%CI: 0.809-0.962), 0.746 (95%CI: 0.631-0.861), 0.843 (95%CI: 0.745-0.941)(all P<0.001). The T2 values in the lateral and middle subregions were positively correlated with the grade of supraspinatus tendon injury (r=0.542, 0.615; both P<0.001), while T1 values and T2 values in the medial subregions were not significantly correlated with the grade of supraspinatus tendon injury (both P>0.05). Conclusion: SyMRI has high clinical application value in the grading of supraspinatus tendon injury, especially T2 value can be used as an effective quantitative parameter for the grading of supraspinatus tendon injury.

[Effect of recombinant human thrombin for hemostasis in liver resection: a randomized controlled phase â ¢ clinical trial].

Objective: To evaluate the hemostatic efficacy, safety and immunogenicity of recombinant human thrombin in the treatment of liver wounds that still ooze after conventional surgical hemostasis. Methods: A multicenter, stratified randomized, double-blind, placebo-controlled phase Ⅲ trial with a planned enrollment of 510 subjects at 33 centers, with a 2∶1 randomization to the thrombin group versus the placebo group. An interim analysis will be conducted after approximately 70% of the subjects have completed the observation period. The primary efficacy endpoint was the rate of hemostasis within 6 minutes at the point of bleeding that could be evaluated. Safety analysis was performed one month after surgery, and the positive rates of anti-drug antibody (ADA) and neutralizing antibody were evaluated. Results: At the interim analysis, a total of 348 subjects had been randomized and received the study drug (215 were male and 133 were female). They were aged 19-69 (52.9±10.9)years. Among them, 232 were in the thrombin group and 116 were in the placebo group, with balanced and comparable demographics and baseline characteristics between the two groups. The hemostasis rate at 6 minutes was 71.6% (95%CI:65.75%-77.36%) in the thrombin group and 44.0% (95%CI: 34.93%-53.00%) in the placebo group, respectively (P<0.001). No grade≥3 drug-related adverse events and no drug-related deaths were reported from the study.No recombinant human thrombin-induced immunologically-enhanced ADA or immunologically-induced ADA was detected after topical use in subjects. Conclusion: Recombinant human thrombin has shown significant hemostatic efficacy and good safety in controlling bleeding during liver resection surgery, while also demonstrating low immunogenicity characteristics.

[Burned-out testicular germ cell tumors: a clinicopathological analysis of three cases].

Objective: To investigate the clinicopathological features and possible mechanisms of burned-out testicular germ cell tumors. Methods: The clinical and imaging data, histology and immunophenotypic characteristics of three cases of burned-out testicular germ cell tumors diagnosed at the Ruijin Hospital, Medical College of the Shanghai Jiaotong University, from 2016 to 2020 were retrospectively analyzed. The relevant literature was reviewed. Results: The mean age of the three patients was 32 years. Case 1 had an elevated preoperative alpha-fetoprotein level (810.18 µg/L) and underwent "radical pancreaticoduodenectomy and retroperitoneal lesion resection" for a retroperitoneal mass. Postoperative pathology showed embryonal carcinoma, which needed to exclude gonadal metastasis. Color Doppler ultrasound showed a solid mass of the right testis, with hypoechoic lesion and scattered calcification in some areas. Case 2 was a "right supraclavicular lymph node biopsy specimen." Chest X-ray showed multiple metastases in both lungs. The biopsy showed metastatic embryonic carcinoma and bilateral testicular color Doppler ultrasound revealed abnormal calcifications in the right testicle. Case 3 showed a cystic mass of the right testis with calcification and solid areas. All 3 patients underwent radical right orchiectomy. Grossly, borders of the testicular scar areas were well defined. Cross sectioning of the tumors showed a gray-brown cut surface and single focus or multiple foci of the tumor. The tumor maximum diameter was 0.6-1.5 cm. Microscopically, lymphocytes, plasma cells infiltration, tubular hyalinization, clustered vascular hyperplasia and hemosiderin laden macrophages were found in the scar. Atrophic and sclerotic seminiferous tubules, proliferation of clustered Leydig cells and small or coarse granular calcifications in seminiferous tubules were present around the scar. Seminoma and germ cell neoplasia in situ were seen in case 1, germ cell neoplasia in situ was seen in case 2 and germ cells with atypical hyperplasia were seen in case 3. Immunohistochemistry showed that embryonic carcinoma expressed SALL4, CKpan(AE1/AE3) and CD30, seminoma and germ cell tumor in situ expressed OCT3/4, SALL4 and CD117, and spermatogenic cells with atypical hyperplasia expressed CD99 and SALL4. The Ki-67 positive index was about 20%, while OCT3/4 and CD117 were both negative. Conclusions: Burned-out testicular germ cell tumors are rare. The possibility of gonad testicular metastasis should be considered first for extragonadal germ cell tumor. If fibrous scar is found in testis, it must be determined whether it is a burned-out testicular germ cell tumor. The burned-out mechanisms may be related to the microenvironment of tumor immune-mediated and local ischemic injury.

[Analysis of the application of radiotherapy facility construction project evaluation standard in health management institutions].

Objective: To investigate the application of GBZ/T 220.2-2009 "The Specification of Radiological Protection Assessment for Occupational Hazard in Construction Project-Part 2: Radiotherapy Facility" in health management institutions, and to understand the scientificity, practicability and problems existing in the implementation of the standard. Methods: The method of multistage stratified sampling and questionnaire survey were used to collect the standard application status among 96 radiological health managers who had participated in the evaluation of radiotherapy facility construction projects in 6 provinces and cities from November 2020 to April 2021. A descriptive statistical analysis method was used to analyze the basic information of the survey object, the knowledge of the standard, the publicity and implementation of the standard. Results: The radiological health management personnel mainly came from health supervision agencies (62.5%, 60/96) , and 86.5% (83/96) were engaged in the pre-evaluation of radiotherapy device construction project and the approval and supervision of control effect evaluation. The awareness rate and training rate of radiological health managers on GBZ/T 220.2-2009 were 88.5% (85/96) and 31.3% (30/96) , respectively. 89.6% (86/96) managers thought it could meet the needs of radiotherapy facility construction project approval or supervision. 49.0% (47/96) of managers believed that the standard needed to be revised. Conclusion: The content of GBZ/T 220.2-2009 is basically scientific and reasonable, but the publicity, implementation and training of radiological health administrator still need to be strengthened. It is suggested to revise some clauses in the standard that do not meet the requirements.

[In vivo study of liposome-modified polyetheretherketone implant on bacteriostasis and osseointegration].

OBJECTIVE: To develop dexamethasone plus minocycline-loaded liposomes (Dex/Mino liposomes) and apply them to improve bioinert polyetheretherketone (PEEK) surface, which could prevent post-operative bacterial contamination, enhance ossification for physiologic osseointegration, and finally reduce implant failure rates. METHODS: Dex/Mino liposomes were covalently grafted onto the PEEK surface using polydopamine (pDA) coating as a medium. Confocal laser scanning microscopy was used to confirm the binding of fluorescently labeled liposomes onto the PEEK substrate, and a microplate reader was used to semiquantitatively measure the average fluorescence intensity of fluorescently labeled liposome-decorated PEEK surfaces. Moreover, the mouse subcutaneous infection model and the beagle femur implantation model were respectively conducted to verify the bioactivity of Dex/Mino liposome-modified PEEK in vivo, by means of micro computed tomography (micro-CT) and hematoxylin and eosin (HE) staining analysis. RESULTS: The qualitative and quantitative results of fluorescently labeled liposomes showed that, the red fluorescence intensity of the PEEK-pDA-lipo group was stronger than that of the PEEK-NF-lipo group (P < 0.05); the liposomes were successfully and uniformly decorated on the PEEK surfaces due to the pDA coating. After mouse subcutaneous implantation of PEEKs for 24 hours, HE staining results showed that the number of inflammatory cells in the PEEK-Dex/Mino lipo group were lower than that in the inert PEEK group (P < 0.05), indicating a lower degree of infection in the test group. These results suggested that the Mino released from the liposome-functionalized surface provided an effective bacteriostasis in vivo. After beagle femoral implantation of PEEK for 8 weeks, micro-CT results showed that the PEEK-Dex/Mino lipo group newly formed more continuous bone when compared with the inert PEEK group; HE staining results showed that more new bones were formed in the PEEK-Dex/Mino lipo group than in the inert PEEK group, which were firmly bonded to the functionalized PEEK surface and extended along the PEEK interface. These results suggested that the Dex released from the liposome-functionalized surface induced effective bone regeneration in vivo. CONCLUSION: Dex/Mino liposome modification enhanced the bioactivity of inert PEEK, the functionalized PEEK with enhanced antibacterial and osseointegrative capacity has great potential as an orthopedic/dental implant material for clinical application.

[Analysis of factors affecting live birth outcome of frozen-thawed embryo transfer cycle].

Objective: To analyze the related factors affecting the success of frozen-thawed embryo transfer (FET). Methods: A total of 563 couples treated in the Reproductive Medicine Center of Guangdong Hospital of Traditional Chinese Medicine from January 2017 to March 2020 were selected as subjects. A total of 736 FET cycles were included to analyze the live birth outcomes of FET. Pregnancy outcomes, pregnancy complications and embryo status of patients between the live birth group and the non-live birth group were compared. A multivariate logistic regression model was used to evaluate the association between the 15 candidate factors and live birth outcomes for identifying independent factors associated with the live birth outcomes of the FET. Results: Among the enrolled subjects, the men were (33±5) years old at sperm extraction while the women were (31±4) years old at ovum pick-up (OPU) and (32±4) years old at embryo transfer (ET) and their infertility duration were (3.5±2.6) years. There were 333 (45.2%) live birth cycles and 403 (54.8%) non-live birth cycles in the 736 FET cycles. Pregnancy complications occurred in 49 cases (14.7%) of the live birth group. The age of the women at ET ((31±4) vs (32±4) years), the age of the women at OPU ((30±4) vs (32±4) years) and the age of the men at sperm extraction ((33±4) vs (34±5) years) in the live birth group were all lower than those in the non-live birth group. The infertility duration was shorter ((3.2±2.2) vs (3.6±2.8) years), and the proportion of primary infertility was higher ((63.1%, 210 cases) vs (49.6%, 200 cases)) in the live birth group (P<0.05) than those in the non-live birth group. Multivariate logistic regression analyses showed that the age of woman at ET (OR (95%CI): 0.50 (0.27-0.92), P=0.026), the types of infertility (0.62 (0.43-0.88), P=0.008), the numbers of optimal embryos transferred (1.60(1.11-2.31), P=0.012), and the types of embryos transferred (2.43 (1.46-4.01), P=0.001) were statistically significant related factors for live birth outcome of FET. Conclusion: The age of the woman at ET, the types of infertility, the numbers of optimal embryos transferred and the types of embryos transferred are associated factors for the outcomes of live birth after FET.

[Clinical application of expanded noninvasive prenatal testing for fetal chromosome abnormalities].

To assess the positive predictive value (PPV) of extended noninvasive prenatal testing (NIPT-plus) for fetal chromosomal abnormalities. This retrospective research enrolled 511 cases of pregnant women with positive NIPT-plus results at the Obstetrics and Gynecology Hospital of Fudan University from May 2017 to January 2021. Karyotype analysis and chromosome microarray analysis (CMA) techniques was applied for verification. All cases were followed to determine their pregnancy outcome. The Chi-square test was used in PPV. 63 out of 511 refused prenatal diagnosis after counseling, 448 pregnant women with prenatal diagnosis showed that the PPVs of NIPT-plus test for fetal trisomy 21, 18 and 13 (T21, T18, T13), sex chromosome aneuploidy (SCAs) and chromosome microdeletion/microduplication syndrome (MMS) were 86.0% (92/107), 79.5% (35/44), 54.5% (12/22), 39.5% (75/190), and 41.7% (30/72), respectively. The results revealed that the PPV was higher among older pregnant women compared to young pregnant women (77.8% vs. 51.9%,P<0.01). With increasing maternal age, the PPV of NIPT-plus presented increasing trends for T21, T13, and composite PPV except for T18 or SCAs. In addition, the termination rates for confirmed SCAs fetal karyotypes 45, X; 47, XXX; 47, XXY and 47, XYY were 11/11, 3/15, 91.7% (22/24) and 1/14, respectively. NIPT-plus can safely and effectively detect fetal chromosomal abnormalities and can be extended to MMS screening, significantly reducing the proportion of interventional prenatal diagnoses, and those with positive screening still require further confirmation.

[Efficacy of drug coated balloon versus conventional balloon in the treatment of coronary de novo bifurcation lesions: a meta-analysis].

Objective: To systematically evaluate the efficacy of drug coated balloon (DCB) versus conventional balloon in the treatment of coronary de novo bifurcation lesions. Methods: The databases of PubMed, Embase, Cochrane Library, Web of science, CNKI (China National Knowledge Infrastructure), Wanfang database, VIP, China Biology Medicine disc, Chinese clinical trial registry, American clinical trial registry and cardiovascular related websites until September 2020 were retrieved for collecting the randomized controlled trials (RCT) comparing DCB versus conventional balloon in the treatment of coronary de novo bifurcation lesions. The risk of bias of included studies was assessed using the Cochrane risk assessment tool. The meta-analysis was performed by using Revman 5.3 and Stata 14.0 software. Results: Seven RCTs with a total of 613 patients were included in this meta-analysis. Among the included studies, 4 articles reached the low risk of bias, and the other 3 articles reached the medium risk of bias. The results of meta-analysis showed that there was no significant difference in the major adverse cardiac events (RR=0.65, 95%CI 0.39-1.08, P=0.10), myocardial infarction (RR=0.68, 95%CI 0.25-1.80, P=0.43), target lesion revascularization (RR=0.94, 95%CI 0.53-1.67, P=0.83) between DCB group and conventional balloon group. Late lumen loss of side branch was less in the DCB group than that in the conventional balloon group (WMD=-0.25, 95%CI -0.41--0.09, P<0.01) and the risk of side branch restenosis was also lower in the DCB group than that in the conventional balloon group (RR=0.47, 95%CI 0.22-0.98, P<0.05). However, subgroup analysis showed that the conclusions of domestic studies and foreign studies on late lumen loss and side branch restenosis were inconsistent. The meta-analysis based on domestic literature showed that the risk of side branch restenosis after DCB treatment was lower compared with conventional balloon group (RR=0.29, 95%CI 0.15-0.57, P<0.05), while this parameter derived from foreign literatures remained unchanged between two groups (P=0.53). The meta-analysis results of domestic literature showed that late lumen loss in DCB group was less than that in conventional balloon group (WMD=-0.32, 95%CI -0.51--0.13, P<0.05), but this phenomenon was not observed in foreign literatures (P=0.30). Conclusions: The use of DCB in the treatment of coronary de novo bifurcation lesions has the potential to reduce the rate of restenosis and late lumen loss of side branch compared with conventional balloon group. However, due to the limitation on quantity, quality and results of published studies, more high-quality and large scale RCTs are still needed to confirm these findings.

[Research progress on the human health risks assessment of radionuclides in water environment].

The quality of the water environment is one of the most important factors that can directly affect the health of human beings and other non-human species. The levels of the radionuclides in water environment are the key indicator while assessing the quality of water environment. Recently, with the development of the nuclear energy in China, the public people have paid a focus attention on the levels and the health risks of the radionuclides. This paper introduced the sources, the health effects, the health risk assessment methods and the current status of the health risk assessment study about the radionuclides, in order to provide basis for the health risk assessment of radionuclides in water environment and the protection of human health.

[Application of five methods in the occupational health risk assessment of workers exposed to welding fumes].

Objective: To assess the health risks of welding fume jobs with five occupational health risk assessment methods, and to compare the advantages, disadvantages and applicability of these methods in the health risk assessment of welding fume. Methods: The International Commission for Mining and Metals (ICMM) occupational health risk assessment method, MES method, the qualitative method and comprehensive index method in GBZ/T 298-2017 "Technical Guidelines for Occupational Health Risk Assessment of Chemical Hazardous Factors in the Workplace" were used to assess the risk of welding fume exposure positions in four manufacturing enterprises in Tianjin in March, 2020. The assessment results of different methods were standardized by risk ratio (RR) . Results: After the results were standardized, the results of enterprises 1, 2 and 4 were negligible risks, enterprise 3 was medium risk in the ICMM matrix method and MES method, and the results of ICMM quantitative method for each enterprise were negligible risk, low risk, extremely high risk and low risk, respectively. The results of the qualitative assessment of the guidelines for all companies were negligible risks, and the comprehensive index method were medium risks. Conclusion: The five models are all suitable for occupational health risk assessment of welding fumes, but they all have certain shortcomings. They should be combined with qualitative and semi-quantitative assessment results for comprehensive analysis.

[Research on the short-term effects of welding fumes on workers' lung function: a panel study].

Objective: To explore the short-term effects of welding fumes on workers' lung function in the welding environment preliminarily, and provide reference for future research. Methods: In October 2020, the lung function of the subjects was repeatedly measured before and after the working shift with a panel study. The paired t test was used to compare the lung function before and after the shift, and the linear mixed effects model was used to analyze the short-term changes of lung function. Results: 36 male welders were included, and the average age was (30.72±5.21) years, average employed year was (4.36±2.17) years. And the average concentration of welding fume was (1.27±0.49) mg/m(3). The forced vital capacity (FVC) , forced expiratory volume in the first second (FEV1) and peak expiratory flow (PEF) of welders after the shift were significantly lower than those before the shift (t=19.52, 48.13, 62.03, P<0.05) . After adjusting the workers' age, BMI and employed years, the changes of FVC% and FEV1% with the concentration of welding fume were statistically significant (ß=-1.02, 95%CI: -1.54--0.52; ß=-1.56, 95%CI: -1.95--1.16; P<0.01) . In another word, for the 1 mg/m(3) increase of welding fume in the working environment, compared with the baseline, the FVC decreases by 1.02%, and FEV1 decreases by 1.56%. Conclusion: Short-term exposure to welding fumes in workplace can reduce the lung function of welders.

Prognostic impact of prognostic nutritional index in advanced (stage IIIB/IV) non-small cell lung cancer patients.

Prognostic nutritional index (PNI) is a parameter reflecting prognosis for various cancers, including resected lung cancer. However, there were few reports to study the relationship between the PNI and overall survival (OS) in patients with advanced (stage IIIB/IV) non-small lung cancer (NSCLC). In this study, we collected the clinical data of 315 patients with advanced (stage IIIB/IV) NSCLC who had received chemotherapy or epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) between January 2010 and June 2011. Survival curves were plotted using the Kaplan-Meier method. Multivariate analyses were used to evaluate prognostic significance of PNI in patients with advanced (stage IIIB/IV) NSCLC. In our analysis, we found that PNI (p=0.001) was significantly associated with OS in patients with advanced (stage IIIB/IV) NSCLC, so was smoking (p<0.001) and disease stage (p=0.005). We demonstrated that PNI could be utilized to predict survival outcomes in patients with advanced (stage IIIB/IV) NSCLC. Patients with a lower PNI may have worse prognosis.

[Trend in proportion and clinicopathological characteristics of young women with stage â a2 to â ¡a2 cervical cancer].

Objective: To analyze the 13 years trend in proportion, risks factors and clinicopathological characteristics of young women with stage Ⅰa2 to Ⅱa2 cervical cancer by using multi-center data of cervical cancer in China. Methods: The clinicopathological data of 46 313 patients with cervical cancer treated from 37 hospitals in China were obtained from January 2004 to December 2016. Using clinical and pathologic data, each patient's stage was reclassified by the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system. A total of 19 041 patients were selected according to the following criteria: FIGO stage Ⅰa2 to Ⅱa2, underwent type B or C radical hysterectomy and pelvic lymphadenectomy. All the patients were divided into two groups: the study group of 1 888 patients aged 35 years or younger and the control group of 17 153 patients aged over 35 years. The 13 years trend in proportion of young women with stage Ⅰa2 to Ⅱa2 cervical cancer, risks factors and clinicopathological characteristics of two groups were retrospectively analyzed. Results: (1) The total number of hospitalized patients with stage Ⅰa2 to Ⅱa2 cervical cancer increased annually. However, a downward trend of patients aged 35 years or younger was observed (P<0.01) . The constituent ratio of patients aged 35 years or younger was significantly greater during 2004-2010 than that during 2011-2016 [12.6% (820/6 484) and 8.5% (1 068/12 557) , respectively; χ(2)=82.101, P<0.01]. (2) Compared with patients aged over 35 years, patients aged 35 years or younger had an earlier age at menarche, a later age at marriage, lesser gravida and parity (all P<0.01). The positive rate of high-risk HPV infection was not statistically different between two groups (all P>0.05). (3) The proportions of stage Ⅰ, exophytic type and non-squamous histological type in patients aged 35 years or younger were clearly higher than those in patients aged over 35 years (83.4% vs 68.5%, P<0.01; 63.2% vs 56.2%, P<0.01; 13.9% vs 12.0%, P<0.05, respectively). Whereas the poor differentiation ratios of the two groups had no statistical significance (P>0.05). (4) As for the postoperative pathological risk factors, the rate of surgical margin involvement in patients aged 35 years or younger was lower than that aged over 35 years (1.1% vs 1.8%, P<0.05), and the rate of depth of stromal invasion >1/2 in patients aged 35 years or younger was lower than that in patients aged over 35 years (40.1% vs 50.9%, P<0.01). In addition, there were no significant difference in parametrial margin involvement, tumor size and lymph vascular space invasion between two groups (all P>0.05). Conclusions: The trend in proportion among hospitalized patients for stage Ⅰa2 to Ⅱa2 cervical cancer in young women is decreasing yearly. Compared with cervical cancer in middle-aged and elderly women, cervical cancer in young women have an earlier age at menarche, a higher proportion of stage Ⅰ patients and non-squamous histological type. In terms of the postoperative pathological risk factors, the rate of surgical margin involvement and depth of stromal invasion >1/2 in young women with cervical cancer are lower than in middle-aged and elderly women.

[The postnatal development of perineuronal net, Nogo receptor and the effect of fluoxetine on remodeling it in the visual cortex of rats].

Objective: To investigate the postnatal development of perineuronal net (PNN), Nogo receptor (Nogo R) in visual development and the effect of fluoxetine(Flx) on remodeling it in the visual cortex of adult rats. Methods: Experimental study. (1) Wistar rats were divided into postnatal weeks (PW)1,PW3,PW5,PW7,PW9 group (8 rats in each group) according to the age of PW. The changes of PNN and Nogo R were observed in the visual cortex of each group. (2) The adult rats (10 weeks after birth) were randomized into Flx 0W, Flx 2W, Flx 4W, Flx 6W and Flx 8W group (8 rats in each group) according to Flx administrational weeks. The influence of Flx on the expression of PNN and Nogo receptor in the visual cortex was detected by immunofluorescence and western blots. (3) The adult rats were randomized into Cont (negative control), Flx, binocular form deprivation(BFD,positive control) and BFD+Flx group (8 rats in each group). Flx group accepted oral administration at the dosage of 0.2 mg/ml once per day for 4 weeks. The eyelids were binocularly sutured for 2 weeks to form the BFD group, and the combination of Flx administration and BFD was performed in the BFD+Flx group.No intervention was conducted in the control group (Cont group). Immunofluorescence was used to observe the expression pattern of PNN staining by biotinylated wisteria floribunda lectin (WFA). The expression of Nogo R in the visual cortex was detected by immunofluorescence and Western blots. The expression of PNN and Nogo R were examined in each group. And t test, analysis of variance and rank sum test were employed for inter-group comparison based on the homogeneity of variance. Bonferroni method was used for multiple comparison and simple linear regression analysis was used for the trend. Results: (1) The expression of PNN (standardized b=0.97, P=0.005) and Nogo R (standardized b=0.96, P=0.010) increased during the postnatal development and the Nogo R reached the matured level at PW7 (PW7 vs. PW9, 131.83±3.78 vs. 135.11±3.92, Z=1.93, P=0.062). (2) Flx significantly decreased PNN in the visual cortex of adult rats. The density of PNN-positive cells in the visual cortex of healthy adult rats fed with Flx for 4 weeks was (86.22±7.68)/mm(2), which was similar to that of 3 weeks old rats [(84.21±6.68)/mm(2), t=2.08, P=0.073]. The expression of PNN (standardized b=-0.88, P=0.040) and it's receptor Nogo R (standardized b=-0.90, P=0.007) decreased with prolongation of Flx use. (3) The expression of Nogo R (t=13.42,11.47, 18.13; P=0.012, 0.013, 0.001; Flx, BFD and BFD+Flx group vs. Cont group) and the density of PNN (t=10.09, 7.64, 13.01; P=0.007, 0.011, 0.001; Flx, BFD and BFD+Flx group vs. Cont group) could be modulated by Flx and BFD after the critical period. There are no differences in BFD and Flx group on Nogo R changes (t=2.41, P=0.153). The expression of Nogo R protein was also different among the 4 groups (H=5.69, P=0.041). The effect of Flx combined with BFD was better than the Flx or BFD alone (Flx vs. BFD+Flx, Z=4.22, P=0.005; BFD vs. BFD+Flx, Z=3.09, P=0.010). Conclusions: The expression of PNN and Nogo R increase during the postnatal development. Chronic Flx treatment decrease the expression of PNN and Nogo R after the critical period in the visual cortex of adult rats, that is the same as BFD. (Chin J Ophthalmol, 2019, 55:37-45).

Behavioural tactic predicts preoptic-hypothalamic gene expression more strongly than developmental morph in fish with alternative reproductive tactics.

Reproductive success relies on the coordination of social behaviours, such as territory defence, courtship and mating. Species with extreme variation in reproductive tactics are useful models for identifying the neural mechanisms underlying social behaviour plasticity. The plainfin midshipman (Porichthys notatus) is a teleost fish with two male reproductive morphs that follow widely divergent developmental trajectories and display alternative reproductive tactics (ARTs). Type I males defend territories, court females and provide paternal care, but will resort to cuckoldry if they cannot maintain a territory. Type II males reproduce only through cuckoldry. We sought to disentangle gene expression patterns underlying behavioural tactic, in this case ARTs, from those solely reflective of developmental morph. Using RNA-sequencing, we investigated differential transcript expression in the preoptic area-anterior hypothalamus (POA-AH) of courting type I males, cuckolding type I males and cuckolding type II males. Unexpectedly, POA-AH differential expression was more strongly coupled to behavioural tactic than morph. This included a suite of transcripts implicated in hormonal regulation of vertebrate social behaviour. Our results reveal that divergent expression patterns in a conserved neuroendocrine centre known to regulate social-reproductive behaviours across vertebrate lineages may be uncoupled from developmental history to enable plasticity in the performance of reproductive tactics.

Anti-nociceptive effects of caloric restriction on neuropathic pain in rats involves silent information regulator 1.

BACKGROUND: Caloric restriction (CR) increases both average and maximum lifespan, retards physiological signs of ageing, and delays the onset of several diseases and may mediate neuropathic pain. Neuropathic pain seriously affects the quality of life of patients. In this study, we investigated whether CR exerts anti-nociceptive effects on neuropathic pain, and probed its potential mechanisms. METHODS: Adult rats were divided into two dietary groups: an ad libitum (AL)-fed group and a CR group, which was provided with 60% of the food intake of AL rats for 6 weeks. The effects of 6-week CR on pain behaviour and neuro-inflammation induced by chronic constriction injury of the sciatic nerve were evaluated. RESULTS: Rats subjected to a CR diet had reduced hypersensitivity to mechanical and thermal stimuli after nerve-constriction injury. CR increased the silent information regulator 1 (SIRT1) expression, and suppressed the nerve-constriction-induced production of mitochondrial-derived reactive oxygen species and activation of nuclear factor kappa B accompanied by suppression of mature interleukin-1ß production in the ipsilateral spinal cord dorsal horn. The inhibition of SIRT1 reversed the effects of caloric restriction on pain behaviours. Moreover, CR decreased the phosphorylation of N-methyl-d-aspartate receptor subunits and the mitogen-activated protein kinase family, decreased the sensory neurone excitability, and inhibited the nerve-constriction-induced glial-cell activation. CONCLUSIONS: These results suggest that the effects of CR on pain behaviours in a rat model of nerve injury are via inhibition of excessive neuro-inflammation induced by the injury. CR may be of benefit in patients with neuropathic pain.

Sperm cystic fibrosis transmembrane conductance regulator expression level is relevant to fecundity of healthy couples.

Cystic fibrosis transmembrane conductance regulator (CFTR) is relevant to sperm quality, sperm capacitation and male fertility. However, it is still unknown whether CFTR can be a potential parameter for fecundity prediction in healthy couples. In this study, 135 healthy couples were divided into groups according to their fertility. We demonstrated that the sperm CFTR expression level of healthy males who never impregnated their partners (49 cases, 38.68 ± 2.71%) was significantly lower than that of fertile men (86 cases, 46.35 ± 2.32%). Sperm CFTR expression level accurately corresponded with fertility through the logistic regression model. Receiver operating characteristic (ROC) curve analysis showed that the cut-off value of sperm CFTR expression level for fecundity prediction was 43.75%. Furthermore, cumulative pregnancy rates (CPRs) of CFTR > 43.75% group and CFTR ≤ 43.75% group during the follow-up periods were 80.6% and 49.3% respectively. Meanwhile, the mean time to pregnancy (TTP) of CFTR ≤ 43.75% group (26.79 ± 2.35) was significantly longer than that of CFTR > 43.75% group (16.46 ± 2.42). Therefore, sperm CFTR expression level is relevant to fecundity of healthy couples and shows potential predictive capacity of fecundity.

[Triptolide reverses apatinib resistance in gastric cancer cell line MKN45 via inhibition of heat shock protein 70].

Objective: To investigate the effect of triptolide, a specific inhibitor of heat shock protein 70 (HSP70), on apatinib resistance in gastric cancer cells line MKN45. Methods: The apatinib-resistant cells (MKN45/AR) and MKN45 parental cells were treated with apatinib, triptolide and apatinib combined with triptolide, respectively. CCK-8 assay was performed to determine the half maximal inhibitory concentration (IC(50)) of MKN45/AR and MKN45 cells in the presence of different treatment. The mRNA expression of heat shock protein gene (HSPA1A and HSPA1B) was detected by RT-PCR, while the protein expression of heat shock protein 70 was analyzed using Western blot in MKN45/AR and MKN45 cells. Results: The IC(50) values of apatinib-sensitive and apatinib-resistant MKN45 cells were 10.411 µmol/L and 70.527 µmol/L, respectively, showing a significant difference (P<0.05). The mRNA expression of HSPA1A and HSPA1B in MKN45/AR cells was significantly higher than that in MKN45 cells (P<0.001). The protein expression of heat shock protein 70 was significantly decreased after 0.25 µmol/L triptolide treatment in MKN45/AR cells (P<0.01). When heat shock protein 70 was inhibited by triptolide, the IC(50) value of apatinib in MKN45/AR cells was reduced to 11.679 µmol/L, which was significantly lower than cells treated with apatinib alone (P<0.05). Conclusions: The apatinib-resistant MKN45 cells have high levels of heat shock protein 70. Low doses of triptolide can significantly inhibit heat shock protein 70, leading to reverse the resistance phenotype of MKN45/AR cells. Therefore, inhibition of heat shock protein 70 provides a new therapy strategy for patients with apatinib resistance.