Measurements of All-Particle Energy Spectrum and Mean Logarithmic Mass of Cosmic Rays from 0.3 to 30 PeV with LHAASO-KM2A.

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15 PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.

[Visual analysis of the current research status and hotspots of electric burns at home and abroad].

Objective: To analyze the literature on electric burns published at home and abroad, and to explore the research hotspots and frontiers of electric burns. Methods: The bibliometric method was used. The Chinese and English literature related to electric burns published in China National Knowledge Infrastructure, Wanfang database, VIP database and the core collection of Web of Science database from January 1, 2013 to December 31, 2022 were searched respectively, and the CiteSpace 6.2.R2 software was used for analysis. The number of papers, authors, countries, and institutions of Chinese and English literature were counted respectively, and the co-occurrence analysis of keywords and mutation analysis and cluster analysis on the basis of the co-occurrence analysis were conducted, besides, the clustering time line figure was obtained after the keywords were sorted by time to explore the current research status and the evolution process of hotspots in the field of electric burns. Results: A total of 398 English papers were retrieved from the core collection of Web of Science database, and a total of 523 Chinese papers were retrieved from China National Knowledge Infrastructure, Wanfang database, and VIP database after duplicate check. From 2013 to 2022, the number of English literature published in the field of electric burns showed a steadily upward trend, and the number of published Chinese literature showed a downward trend and tended to be stable. In Chinese literature, a total of 302 authors as the first author published papers related to electric burns, with 17 core authors published ≥3 papers; in English literature, a total of 320 authors as the first author published papers related to electric burns. Researches on electric burns were carried out in 65 countries, with United States having the most cooperation with other countries and the largest number of papers published. A total of 512 institutions at home and abroad published papers related to electric burns, and the institutions with the largest number of Chinese and English papers were Shanghai Electric Power Hospital in China (n=14) and Hallym University in Korea (n=11), respectively. A total of 1 176 Chinese keywords and 1 068 English keywords were included for co-occurrence analysis after excluding keywords related to the searching words. The top three keywords in frequency in Chinese literature were surgical flap, wound repair, and nursing, and the top three keywords in frequency in English literature were management, epidemiology, and children. Ten clusters were obtained by keyword analysis in Chinese literature, and the largest cluster was wound healing, followed by clinical effects and surgical flaps. Seven clusters were obtained by keyword analysis in English literature, and the largest cluster was reconstructive surgical procedures, followed by chronic pain and shock. The persistent clusters in Chinese literature were wound healing and clinical outcomes, etc., and the prominent nodes in the recent two years were surgical timing, limb electric burns, and hypertrophic scars; the persistent clusters in English literature were reconstructive surgical procedures and chronic pain, etc., and the prominent nodes in the recent two years were predictors and burn management, etc. In Chinese literature, the keyword with the longest duration of mutation (2017-2021) was wrist electric burns, and the keyword with the highest intensity of mutation was flap repair; in English literature, the keyword with the longest duration of the mutation (2019-2022) was voltage, and the keyword with the highest intensity of mutation was prevention. Conclusions: There are similarities and differences in the research directions and hotspots of electric burns at home and abroad. Surgical flap repair is a common research hotspot at home and abroad. At present, domestic research focuses on wound healing, wrist electric burns, and other aspects, while international research focuses on treatment management, epidemiology, reconstruction, and other aspects.

[Influence of work engagement and self-efficacy of nurses on clinical practice ability in burn intensive care unit].

Objective: To analyze the influence of work engagement and self-efficacy of nurses on clinical practice ability in burn intensive care unit (BICU), and to explore its potential pathways of action. Methods: A cross-sectional survey was conducted. From May to October 2020, a total of 30 hospitals with BICU in China were selected by stratified sampling method. Among BICU nurses who met the inclusion criteria, their clinical practice ability, work engagement, and self-efficacy were evaluated by self-evaluation scale of oriented problem-solving behavior in nursing practice (OPSN), Utrecht work engagement scale (UWES), and general self-efficacy scale (GSES), respectively. The total scale scores of each index and the average item scores were recorded. The self-designed general data questionnaire was used to investigate the nurses' gender, age, marital status, education background, working years, professional title, and the economic region of the hospital that they belonged to. The total scale scores of the above-mentioned three evaluation indexes were compared after the classification of nurses according to general data, and the data were statistically analyzed with independent sample t test or one-way analysis of variance. Pearson correlation analysis was used to analyze the correlation between the total scale scores of the three evaluation indexes. Based on the total scale scores of the above-mentioned three evaluation indexes, a structural equation model was established, the mediation analysis of the relationship among the three evaluation indexes and the pathway analysis of the structural model were conducted, and the Bootstrap method was used to verify the pathways of action. Results: A total of 401 questionnaires were distributed, and 337 valid questionnaires were returned, with a valid return rate of 84.04%. The total scale scores of clinical practice ability, work engagement, and self-efficacy of 337 nurses were 98.2±11.7, 67.7±18.6, and 26.6±5.6, respectively, and the average item scores were 3.9±0.5, 4.5±1.2, and 2.7±0.6, respectively. Among the 337 nurses, the majority were female, aged 40 or below, married, and had a bachelor's degree with work experience of ≤10 years; both nurses with professional nurse title and nurses from the Southeast region accounted for about 50%. There were statistically significant differences in the total scale score of clinical practice ability among nurses with different ages, education backgrounds, working years, and professional titles (with F values of 3.26, 4.36, 3.12, and 2.80, respectively, P<0.05). There was statistically significant difference in the total scale score of work engagement among nurses with different working years (F=4.50, P<0.05). There were statistically significant differences in the total scale score of self-efficacy among nurses with different ages, working years, and professional titles (with F values of 4.91, 4.50, and 2.91, respectively, P<0.05). The total scale score of nurses' work engagement was significantly positively correlated with the total scale score of clinical practice ability and the total scale score of self-efficacy (with r values of 0.30 and 0.51, respectively, P<0.05). The total scale score of nurses' self-efficacy was significantly positively correlated with the total scale score of clinical practice ability (r=0.37, P<0.05). The model had good adaptability, and the intermediary model was established. Nurses' work engagement had a significantly positive effect on both self-efficacy and clinical practice ability (with ß values of 0.54 and 0.16, respectively, P<0.05), and nurses' self-efficacy had a significantly positive effect on clinical practice ability (ß=0.29, P<0.05). Work engagement had a direct effect on self-efficacy and clinical practice ability, and self-efficacy had a direct effect on clinical practice ability and played a mediating role between work engagement and clinical practice ability. Bootstrap validation showed that self-efficacy played a significantly mediating role in the influence of work engagement on clinical practice ability (with effect size of 0.16, with 95% confidence interval of 0.08-0.24, P<0.05), accounting for half of the total effect of work engagement on clinical practice ability (with effect size of 0.32). Conclusions: BICU nurses have an above-average level of clinical practice ability, a medium level of self-efficacy, and a high level of work engagement. Work engagement and self-efficacy are positively correlated with clinical practice ability. Work engagement can directly affect clinical practice ability or indirectly affect clinical practice ability through the mediating role of self-efficacy.

[Associations of genetic variations in pyroptosis related genes with acute adverse events in postoperative rectal cancer patients receiving concurrent chemoradiotherapy].

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.

Effect of ontological insecurity on vaccination behavior against COVID-19: a hospital-based cross-sectional study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has brought great uncertainty to our society and it may have disrupted people's ontological security. Consequently, this hospital-based study concerns the impact of ontological insecurity on vaccination behavior against COVID-19. STUDY DESIGN: This cross-sectional study was conducted among hospital inpatients. METHODS: A questionnaire survey addressing inpatient ontological insecurity and vaccination behavior against COVID-19 was administered in Taizhou, China. A total of 1223 questionnaires were collected; specifically, 1185 of them were credible, for a validity rate of 96.9%. RESULTS: The score of ontological insecurity was 13.27 ± 7.84, which was higher in participants who did not recommend vaccination for others than those who did (12.95 ± 8.25 vs 14.00 ± 6.78, P = 0.022). There was no difference between the vaccinated and unvaccinated groups (13.22 ± 7.96 vs 13.35 ± 7.67, P = 0.779). Lower ontological insecurity (odds ratio [OR] = 1.40, 95% confidence interval [CI]: 1.08-1.81) and being inoculated with COVID-19 vaccines (OR = 2.17, 95% CI: 1.67-2.82) were significantly associated with recommendation of COVID-19 vaccines to others after adjusting for sex, age, education, and occupation. Associations between low ontological insecurity and recommendations for COVID-19 vaccines were observed in men, adults aged 18-59 years, non-farmers, and vaccine recipients. CONCLUSIONS: This study suggests that the ontological insecurity of participants affects their behavior of recommending the COVID-19 vaccination to others rather than getting vaccinated themselves. This promotion of vaccination can be considered from the perspective of improving ontological security in China.

Clinical characteristics of very late-onset neuromyelitis optica spectrum disorder.

BACKGROUND: The typical age at onset of neuromyelitis optica spectrum disorder (NMOSD) is between 30 and 40 years. A growing awareness about the disease and advances in diagnostic techniques have led to an increase in the number of patients being diagnosed with very late-onset (VLO) NMOSD. This study compared the clinical characteristics, treatments, and prognoses between patients with VLO-NMOSD or late-onset (LO) NMOSD. METHODS: Patients in our study were assigned to two groups based on age at onset of the disease: LO-NMOSD (50-70 years old at onset) and VLO-NMOSD (> 70 years old at onset). We compared clinical characteristics, magnetic resonance imaging of lesions, prognosis, and treatments between the two groups. RESULTS: We collected data from 12 VLO-NMOSD patients with a median age at onset of 74.0 years (interquartile range, 72.6-75.9 years) and 104 LO-NMOSD patients with a median age at onset of 56.0 years (55.8-57.9 years). There were a high proportion of female patients in both the VLO-NMOSD group (9, 75.0%) and the LO-NMOSD group (91, 87.5%). Our study indicated that VLO-NMOSD patients had significantly higher expanded disability status scale (EDSS) scores (8.5 vs 4.0, p = 0.01), higher motor disability rates (41.7% vs 9.6%, p = 0.002), and higher mortality rates (25.0 vs 4.8%, p = 0.044) at last follow-up. However, patients with VLO-NMOSD had lower rates of immunosuppressant usage (50.0% vs 76.9%, p = 0.044). Age at onset was positively correlated with EDSS score at remission (r = 0.49, p < 0.001). CONCLUSION: VLO-NMOSD was associated with higher EDSS score at remission, higher rates of mortality and motor disability, but lower rates of immunosuppressive treatment usage than LO-NMOSD. Future studies are needed to understand the effects of NMOSD on older patients, and to seek suitable treatment to improve their prognosis.

[Therapeutic efficacy analysis of immunotherapy in small cell lung cancer].

Objective: Recently, increasing number of lung cancer patients benefit from immune-checkpoint inhibitors (ICIs). However, the data of Chinese small cell lung cancer (SCLC) patients is limited. This study aims to analyze the response and survival data of ICIs treatment in SCLC and to explore the predictive biomarkers. Methods: Forty-seven SCLC patients who received ICIs treatment from Peking University Cancer Hospital from May 2017 to September 2019 was recruited. Clinical characteristics including sex, age, smoking status, ICIs strategy, PD-L1 expression and therapeutic efficacy were collected to explore the clinical predictive biomarkers for SCLC ICIs treatment. Results: Among the 47 patients, 18 (38.3%) cases were partial repose (PR), 11 (23.4%) were stable disease (SD), 18 (38.3%) were progressive disease (PD), and the objective response rate (ORR) was 38.3%, disease control rate (DCR) was 61.7%, the median progression-free survival (PFS) was 5.3 months. ICIs monotherapy accounts for 27.7%, the ORR was 15.4%, DCR was 53.8%, median PFS was 2.7 months. Combined therapy accounts for 72.3%, the ORR was 47.1%, DCR was 64.7%, median PFS was 5.4 months. Fourteen (29.8%) patients received ICIs as the first line treatment, their ORR was 85.7%, DCR was 100%, median PFS was 9.1 month. The ORR was not related to the age, sex, body mass index (BMI), smoking status and programmed death-ligand 1 (PD-L1) expression (P>0.05). The ORRs were higher in patients underwent PD-L1 monotherapy (P=0.001), combined therapy (P=0.002) and received ICIs as the first line treatment (P<0.001). Log-rank analysis indicated that the PFS of female patients were 12.0 months, significantly longer than 4.4 months of male patients in ICIs treatment (P=0.038). Patients who received PD-L1 monotherapy, combined treatment, or ICIs as the first line treatment had longer PFS than their counterparts, though no statistical significant was observed (P>0.05). Cox multivariate analysis showed that, the gender was not an independent predictor for PFS in ICIs treatment (HR=3.777, 95%CI=0.974~30.891, P=0.054). Conclusions: Immunotherapy is an effective treatment strategy for SCLC. Patients who receive combined ICIs treatment, first line ICIs treatment and PD-L1 treatment may get greater benefits. PD-L1 expression cannot predict the response and PFS in SCLC ICIs treatment.

[Genetic variations in apoptosis genes are associated with acute adverse events in postoperative rectal cancer patients receiving concurrent chemoradiotherapy].

Objective: To investigate the associations between the genetic variations of apoptosis genes and the adverse events of postoperative concurrent chemoradiotherapy in patients with rectal cancer. Methods: We enrolled 362 patients with stage Ⅱ to Ⅲ rectal cancer who received concurrent chemoradiotherapy. Whole blood sample (2 ml) was collected from patient at the time of enrollment before therapy. Sequenom MassARRAY was used to detect the genotypes of 29 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight apoptosis genes, including Fas cell surface death receptor(FAS), Fas ligand(FASL), apoptotic peptidase activating factor 1(APAF1), BCL2 associated X(BAX), TNF-related apoptosis-inducing ligand(TRAIL), TNF-related apoptosis-inducing ligand receptor 1(TRAILR1), TNF-related apoptosis-inducing ligand receptor 2(TRAILR2) and caspase-7(CASP7). The associations between genotypes and adverse events of chemoradiotherapy were measured by unconditional logistic regression model. Results: Three hundred and sixty two patients were treated with total mesorectal excision surgery followed by a total radiation dose of 50 Gy applied in 25 fractions over a period of 5 weeks concurrently with daily administration of capecitabine (1 600 mg/m(2) per day, continuously for 2 weeks and taking a week off every 21-day cycle). One hundred and six patients (29.3%) had grade≥2 myelosuppression. Three SNPs associated with the risk of grade ≥2 myelosuppression included FAS rs1468063 (OR=1.51, 95% CI: 1.07-2.15, P=0.020), APAF1 rs11296996 (OR=0.69, 95% CI: 0.49-0.98, P=0.039) and BAX rs4645904 (OR=0.69, 95% CI: 0.50-0.97, P=0.030). One hundred and sixty one patients (44.5%) developed grade≥2 diarrhea. Five SNPs that significantly associated with risk of grade≥2 diarrhea included APAF1 rs11296996 (OR=1.42, 95% CI: 1.02-2.00, P=0.040), rs74619561 (OR=2.16, 95% CI: 1.27-3.68, P=0.005), CASP7 rs12263370 (OR=1.67, 95% CI: 1.05-2.66, P=0.029), rs12247479 (OR=1.85, 95% CI: 1.12-3.08, P=0.017) and TRAIL rs112822654 (OR=0.68, 95% CI: 0.48-0.96, P=0.027). The remaining SNPs were not related to the adverse events of chemoradiotherapy (all P>0.05). Grade≥2 myelosuppression occurred less frequently in male than in female (P=0.046); Surgical treatment and tumor location had great impact on the occurrence of grade≥2 diarrhea (all P<0.001) and dermatitis (all P<0.05). Conclusions: The genetic variations of FAS, APAF1, BAX, TRAIL and CASP7 are related to the adverse events of concurrent chemoradiotherapy in patients with rectal cancer, which may be potential genetic biomarkers for individualized treatment of rectal cancer.

Overall adjustment acupuncture for postmenopausal osteoporosis (PMOP): a study protocol for a randomized sham-controlled trial.

BACKGROUND: Osteoporosis is becoming more prevalent in aging societies worldwide, and the economic burden attributable to osteoporotic fractures is substantial. The medications presently available to treat osteoporosis have side effects. Acupuncture is widely used for treating osteoporotic postmenopausal women because it is non-invasive and has fewer side effects, but the powerful clinical evidence for its efficacy remains insufficient. Our study intends to explore the effect of overall adjustment acupuncture (OA) in the treatment of postmenopausal osteoporosis (PMOP). METHODS/DESIGN: This study is a randomized, sham-controlled, patient- and assessor-blinded trial and aims to evaluate the effect of OA in women with PMOP. We will recruit 104 women aged 45-70 years with a diagnosis of PMOP. Participants will be randomly allocated in a 1:1 ratio to the OA group and the sham acupuncture (SA) group. Both groups will receive real herbal medicine treatment as a basic treatment twice a day for 3 months, the OA group receives real acupuncture treatment and the SA group receives placebo acupuncture treatment (non-penetrating, sham skin-needle therapy, sham cupping). All patients will receive acupuncture treatment twice per week for 3 months. The primary outcome is bone mineral density (BMD) and the secondary outcomes include estradiol (E2), follicle-stimulating hormone (FSH), bone gla protein (BGP), bone alkaline phosphatase (BALP), total antioxidant capacity (TAC), advanced oxidation protein products (AOPP), PPARγ, ß-catenin, FoxO3a levels, visual analog pain scale score (VAS), Traditional Chinese medicine (TCM) syndrome scores and quality of daily life score (QOL). Outcome measures will be collected at baseline, middle of the treatment (1.5 months), the end of treatment (3 months). The present protocol followed the SPIRIT guidelines and fulfills the SPIRIT Checklist. CONCLUSION: This study will be conducted to compare the efficacy of OA versus SA. This trial should help to evaluate whether OA can effectively prevent and treat PMOP by improving the estrogen levels of postmenopausal women. The mechanism is to improve the imbalance of osteogenic differentiation and lipogenesis of bone-marrow cells under oxidative stress. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR1800017581. Registered on 5 August 2018. URL: http://www.chictr.org.cn.

[Novel compound heterozygous LoF mutations in SRD5A2 may result in disorders of sex development].

Objective: To investigate the novel genetic cause associated with hypospadias and the strategy for preventing offspring genetic defects in these patients. Methods: In March 2019, a patient with gonadal dysplasia (hypospadias associated with cryptorchidism) was referred to Shanghai General Hospital. His secondary sex characters, level of sex hormones and the development of male reproductive system was assessed through physical examination, sex hormone examination, male reproductive system B-ultrasound and computed tomography (CT). Whole-exome sequencing (WES) was preformed to investigate the pathogenic genetic variations associated with hypospadias and cryptorchidism. Also, Sanger sequencing was conducted to verify the WES results in the pedigree. Semen analysis was used to assess the fertility of the proband and the SRD5A2 gene analysis of his spouse was performed to assess the risk of genetic defects in the offspring. Results: The patient suffered from gonadal dysplasia (hypospadias associated with cryptorchidism). Physical examination showed an inverted triangular distribution of pubic hair, small penis and the volume of the testis was 8 ml. Sex hormone examination revealed the level of FSH, LH, Pituitary prolactin (PRL), estrogen (E(2)), testosterone (T), and sex hormone-binding globulin (SHBG) was 25.81 U/L, 10.84 U/L, 21.09 µg/L, 153 pmol/L, 16.95 nmol/L, and 36.15 nmol/L respectively. B-ultrasound and computed tomography (CT) showed left inguinal testis. Also, semen analysis illustrated that the volume was 0.05 ml and sperm concentration<2×10(6)/ml, suggesting oligospermia in this case. WES sequencing and Sanger sequencing showed compound heterozygous LoF mutations in SRD5A2 [NM_000348.3:C.679C>T(p.Arg227Ter) and NM_000348.3:C.16C>T(p.Gln6Ter)] in this patient. And there were no pathogenic genetic variations of SRD5A2 in the spouse. Conclusion: Novel compound heterozygous LoF mutations in SRD5A2[NM_000348.3:C.679C>T(p.Arg227Ter) and NM_000348.3:C.16C>T(p.Gln6Ter)] may be the primary cause of disorders of sex development.

Different Proteins Regulated Apoptosis, Proliferation and Metastasis of Lung Adenocarcinoma After Radiotherapy at Different Time.

INTRODUCTION: The biological changes after irradiation in lung cancer cells are important to reduce recurrence and metastasis of lung cancer. To optimize radiotherapy of lung adenocarcinoma, our study systematically explored the mechanisms of biological behaviors in residual A549 and XWLC-05 cells after irradiation. METHODS: Colony formation assay, cell proliferation assay, cell migration assay, flow cytometry, BALB/C-nu mice xenograft models and Western blot of pan-AKT, p-Akt380, p-Akt473, PCNA, DNA-PKCS, KU70, KU80, CD133, CD144, MMP2 and P53 were used in our study to assess biological changes after irradiation with 0, 4 and 8 Gy at 0-336 hr after irradiation in vitro and 20 Gy at transplantation group, irradiated transplantation group, residual tumor 0, 7, 14, 21, and 28 days groups in vivo. RESULTS: The ability of cell proliferation and radiosensitivity of residual XWLC-05 cells was better than A549 cells after radiation in vivo and in vitro. MMP-2 has statistical differences in vitro and in vivo and increased with the migratory ability of cells in vitro. PCNA and P53 have statistical differences in XWLC-05 and A549 cells and the changes of them are similar to the proliferation of residual cells within first 336 hr after irradiation in vitro. Pan-AKT increased after irradiation, and residual tumor 21-day group (1.5722) has statistic differences between transplantation group (0.9763, p=0.018) and irradiated transplantation group (0.8455, p=0.006) in vivo. Pan-AKT rose to highest when 21-day after residual tumor reach to 0.5 mm2. MMP2 has statistical differences between transplantation group (0.4619) and residual tumor 14-day group (0.8729, p=0.043). P53 has statistical differences between residual tumor 7-day group (0.6184) and residual tumor 28 days group (1.0394, p=0.007). DNA-PKCS has statistical differences between residual tumor 28 days group (1.1769) and transplantation group (0.2483, p=0.010), irradiated transplantation group (0.1983, p=0.002) and residual tumor 21 days group (0.2017, p=0.003), residual tumor 0 days group (0.5992) and irradiated transplantation group (0.1983, p=0.027) and residual tumor 21 days group (0.2017, p=0.002). KU80 and KU70 have no statistical differences at any time point. CONCLUSION: Different proteins regulated apoptosis, proliferation and metastasis of lung adenocarcinoma after radiotherapy at different times. MMP-2 might regulate metastasis ability of XWLC-05 and A549 cells in vitro and in vivo. PCNA and P53 may play important roles in proliferation of vitro XWLC-05 and A549 cells within first 336 hr after irradiation in vitro. After that, P53 may through PI3K/AKT pathway regulate cell proliferation after irradiation in vitro. DNA-PKCS may play a more important role in DNA damage repair than KU70 and KU80 after 336 hr in vitro because it rapidly rose than KU70 and KU80 after irradiation. Different cells have different time rhythm in apoptosis, proliferation and metastasis after radiotherapy. Time rhythm of cells after irradiation should be delivered and more attention should be paid to resist cancer cell proliferation and metastasis.

MAGI1-IT1 stimulates proliferation in non-small cell lung cancer by upregulating AKT1 as a ceRNA.

OBJECTIVE: This study aims to illustrate the potential role of MAGI1-IT1 in the progression of non-small cell lung cancer (NSCLC) and the underlying mechanism. PATIENTS AND METHODS: The relative level of MAGI1-IT1 in normal lung tissues and NSCLC tissues was determined. Its level in NSCLC patients with different tumor sizes (<5 cm or >5 cm), metastatic statues (positive or negative), and tumor staging (stage I+II or stage III+IV) was detected as well. The prognostic potential of MAGI1-IT1 in evaluating the overall survival (OS) and progression-free survival (PFS) of NSCLC patients was assessed by the Kaplan-Meier method. In A549 and PC-9 cells, the regulatory effect of MAGI1-IT1 on the proliferative ability was examined by the cell counting kit-8 (CCK-8), colony formation, and 5-Ethynyl-2'-deoxyuridine (EdU) assay. The target miRNA of MAGI1-IT1 and the target gene binding to miRNA-512-3p were predicted using the Diana database. The interactions among MAGI1-IT1/miRNA-512-3p/AKT1 regulatory loop were tested by the Dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. At last, the rescue experiments were carried out to uncover the regulatory effect of MAGI1-IT1/AKT1 axis on NSCLC progression. RESULTS: MAGI1-IT1 was upregulated in NSCLC tissues. Its level was higher in NSCLC patients with larger tumor size, positive metastasis, or advanced stage. High level of MAGI1-IT1 predicted worse OS and PFS in NSCLC patients. The knockdown of MAGI1-IT1 remarkably attenuated the proliferative ability in A549 and PC-9 cells. MAGI1-IT1 could target miRNA-512-3p, and AKT1 was the target gene of miR-512-3p. The overexpression of AKT1 stimulated lung cancer cells to proliferate. Of note, the elevated proliferative rate in lung cancer cells overexpressing AKT1 was reversed by the silence of MAGI1-IT1. CONCLUSIONS: MAGI1-IT1 is upregulated in NSCLC tissues and cell lines, and predicts a poor prognosis in NSCLC patients. MAGI1-IT1 stimulates proliferative ability in NSCLC by upregulating the AKT1 level by binding to miRNA-512-3p.

MiR-155 inhibits proliferation, invasion and migration of melanoma via targeting CBL.

OBJECTIVE: Malignant melanoma (MM), the deadliest form of skin malignancy, is a highly aggressive and malignant tumor with an increasing incidence rate in recent years. Increasing evidence suggested that dysfunctions of microRNAs (miRNAs) may play an important role in human tumors. However, the effect of miR-155 on malignant melanoma cell migration and invasion remains largely elusive. This research was designed to evaluate the potential function of miR-155 and CBL (Casitas B-lineage lymphoma) in malignant melanoma. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was utilized to detect miR-155 and CBL expression in malignant melanoma tissues and cell lines. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was performed to examine the regulation of miR-155 in melanoma proliferation. Transwell assay was carried out to detect the effect of miR-155 on the MM cell migration and invasion. Luciferase assay and biological analysis were used to predict and determine the target gene of miR-155. RESULTS: miR-155 was down-regulated in malignant melanoma tissues and cell lines. Ectopic expression of miR-155 could inhibit migration and invasion in malignant melanoma cells. What's more, we found that CBL was a new target of miR-155. Additionally, CBL was negatively associated with miR-155 in malignant melanoma and overexpression of CBL attenuated miR-155-mediated inhibition on MM cell migration and invasion. CONCLUSIONS: miR-155 inhibited malignant melanoma proliferation, migration and invasion. And high CBL expression was observed in MM tissues. This newly identified miR-155/CBL axis may provide new insight into the pathogenesis of malignant melanoma.

[Clinical analysis of 43 cases of retroperitoneal laparoscopic renal biopsy].

Objective: Percutaneous renal biopsycurrently is the most important and widely used method of renal biopsy. However, there still are some patients in whom a percutaneous approach may be considered a major risk. In these patients, renal biopsy under direct vision is a reliable alternative. We described our personal technique and experience in a series of Chinese patients who underwent retroperitoneal laparoscopic renal biopsy. Methods: We retrospectively reviewed the patients who had performed retroperitoneal laparoscopic renal biopsy over a 4-year period (Jan 2013 to Jan 2017).Forty-three patients with renal dysfunction were involved inour center.Especially some patients showed atrophic kidney and poor visualization on ultrasonography. The patients' abnormal conditions includeddialysis (10 cases), morbid obesity (5 cases), deaf-mutes (2 cases) and uncontrolled severe hypertension. The kidney was approached via alaparoscopic retroperitoneal route using athree-ports technique. Then biopsies were performed bya 16-gaugebiopsy needle, and hemostasis was achieved by compression.In less cases, a topical spray hemostatic gel was required. Results: Biopsy was performed successfully in all cases and adequate renal tissue was acquired.Mean operative time was 59.4 minutes, mean blood loss was 36.5 ml.Under general anesthesia, no anesthetic accidents and related complications were recorded. Forty-onepatients were discharged within 24 h after operation. Onepatient occurred disseminated intravascular coagulationduring operation. Red blood cell transfusion and fresh-frozen plasma infusion were performed. Injury at hilum of kidney was detected in another patient. And extrapyelogenic repair surgery was performed. Conclusions: The retroperitoneallaparoscopic renal biopsy is a safe, reliable, minimallyinvasive alternative renal biopsy method with better haemostasis, fewer complications and a rapid recovery. As the helpful supplement of percutaneous renal biopsy, this technique may have to be used more often in the future.

Morphological and molecular characterization of Megalobatrachonema hainanensis sp. nov. (Nematoda: Ascaridida), with phylogenetic position of Megalobatrachonema in Cosmocercoidea.

The genus Megalobatrachonema is a rare group of nematode parasites within Ascaridida. The systematic status of Megalobatrachonema in the superfamily Cosmocercoidea (Ascaridida) has long been controversial. The relationship of Megalobatrachonema and Chabaudgolvania remains unsolved. In the present study, a new species of Megalobatrachonema, M. hainanensis sp. nov., was described based on specimens collected in Amolops hainanensis (Boulenger) and Hylarana spinulosa (Smith) (Amphibia: Anura) from Hainan Island, China. The large ribosomal DNA (28S) and internal transcribed spacer (ITS1-5.8S-ITS2) were also sequenced for molecular identification and phylogenetic study. Phylogenetic analyses using maximum likelihood (ML) inference and Bayesian inference (BI) based on 28S and ITS1 sequence data, respectively, supported that Megalobatrachonema is a member of the family Kathlaniidae. In addition, the genetic comparison and phylogenetic results based on ITS1 sequence data also supported that the genus Chabaudgolvania should be considered as a synonym of Megalobatrachonema.

[Efficacy and safety study of microsurgical varicocelectomy in the treatment of non-obstructive azoospermia with varicocele].

Objective: To discuss the efficacy and safety of subinguinal microsurgical varicocelectomy in the treatment of non-obstructive azoospermia (NOA) with varicocele. Methods: The clinical data of 141 patients with NOA and varicocele who underwent subinguinal microsurgical varicocelectomy from March 2015 to June 2017 in Shanghai General Hospital was collected.One hundred and ten patients suffered from varicocele on the left side, 1 on the right side, and the rest (30 cases) were bilateral varicocele. Grade Ⅰ varicocele were found on 7 sides (the right and left side was count respectively), grade Ⅱ on 121 sides, and grade Ⅲ on 43 sides. Sperm analysis, pregnancy rate and complications were recorded after at least 6 months since operation. Results: Eleven cases were lost during the follow-up. Eighteen of the remaining 130 NOA patients processed successful sperm retrieval in post-operative semen analysis (18/130, 13.8%). Six couples(6/130, 4.6%) succeeded in natural pregnancy. Five couples (5/130, 3.8%)underwent successful pregnancy following with intracytoplasmic sperm injection(ICSI). Twenty-six out of the remaining 112 patients underwent the micro dissection testicular sperm extraction (micro-TESE), and 4 patients got a successful sperm retrieval (4/26, 15.4%). Among them, 2 couples had successful pregnancy with ICSI. Totally 2 cases of postoperative infection of incision were found. Conclusions: Microsurgical varicocelectomy had a beneficial effect on sperm quality of patients suffered from NOA with varicocele to some extent, even leading to unassisted pregnancy or avoiding micro-TESE before ICSI. Microsurgical varicocelectomy could be applied in the treatment of NOA with varicocele.

[Investigation and analysis of health-related quality of life in myasthenia gravis patients with myasthenia gravis quality of life-15 Chinese version].

OBJECTIVE: To investigate the level and influencing factors of health-related quality of life in myasthenia gravis (MG) patients with myasthenia gravis quality of life-15 (MGQOL-15) Chinese version and to provide corresponding measures in one tertiary hospital of Sichuan Province. METHODS: We collected the general data (gender, age, body mass index BMI, marital status, educational level and employee status), clinical data [Osserman type, myasthenia gravis composite (MGC), other immunopathies, disease duration, frequency of outpatient visits per month, ratio of disease cost to income each month and frequency of symptoms during the past month] and the MGQOL-15 Chinese version from 168 myasthenia gravis patients in one tertiary hospital of Sichuan Province. RESULTS: The mean score of MGQOL-15 was 17.67±12.78. The score of the item "My occupational skills and job status have been negatively affected." was the highest, followed by "I have trouble using my eyes." and "I am frustrated by my MG." Single factor analysis showed that MG patients' QOL were different with different disease severity MGC (F=19.353, P<0.001), ratio of disease cost to income each month (F=5.831, P<0.001) and the frequency of symptoms during the past month (F=9.128,P<0.001). Multiple regression analysis showed that disease severity MGC (ß=0.743,P<0.001), ration of disease cost to income each month (ß=3.347,P<0.001) and the frequency of symptoms during the past month (ß=2.216,P<0.003) were the main predictors of HRQOL in the MG patients. CONCLUSION: Our study showed that the MGQOL-15 is helpful for clinicians to evaluate MG patients' QOL regularly, investigate the influencing factors and implement corresponding interventions the so as to improve the patients' quality of life. Disease severity MGC, ratio of disease cost to income each month and the frequency of symptoms during the past month were the main predictors of MG patients' QOL. Clinicians should pay more attention to MG patients' disease severity MGC and the frequency of symptoms during the past month.