[Organ preservation in locally advanced colorectal cancer with microsatellite instability-high after immunotherapy].

Neoadjuvant immunotherapy has achieved exciting efficacy with high clinical complete response (cCR) and pathologic complete response (pCR) rates and durable long-term effects. PD-1 checkpoint blockade-based immunotherapy has been highly successful in microsatellite instability high (MSI-H)/mismatch repair deficiency (dMMR) colorectal cancer and has been recommended as the first-line treatment for metastatic colorectal cancer by domestic and international guidelines. Several studies have shown that immunotherapy can be a potentially curable treatment for MSI-H rectal cancer and has even shown promise in organ preservation in colon cancer. In this study, we first clarified the feasibility of the watch-and-wait strategy after PD-1 checkpoint blockade treatment by indirect and direct evidence. Then from the assessment tools (including digital rectal examination, endoscopy, radiology, and lymph node assessment), the viable assessment methods of cCR for immunotherapy and related difficulties are proposed. Finally, the medication choices of immunotherapy, the treatment regimen, and the follow-up strategy are further discussed. We hope that neoadjuvant immunotherapy could be appropriately applied in MSI-H/dMMR colorectal cancer so that more patients can achieve organ preservation.

[Clinical implications of thrombolytic therapy for patients with acute intermediate-high risk pulmonary embolism in Tibet plateau, China].

At present, clinical studies and case reports of systemic thrombolytic therapy for patients with acute pulmonary embolism in Tibet Plateau are very rare. There is little understanding of the risk factors, clinical characteristics, and thrombolytic therapy for patients with acute pulmonary embolism at intermediate-high risk in Tibet Plateau. In this paper, we reported the data of 4 patients with acute intermediate-high risk pulmonary embolism treated with thrombolytic therapy in Lhasa People's Hospital. The demographic characteristics, clinical manifestations, treatment, and outcomes were analyzed. We summarized the clinical features and raised scientific issues. We aimed to provide basic data to improve the standardized diagnosis and treatment of acute pulmonary embolism in plateau, and to point out the direction of future clinical research in this field.

[Analysis of verification results of protective effects of hearing protectors in different industries].

Objective: To get insight into the current practice of noise reduction effect of workers as they wore hearing protectors in different domestic enterprises and the possible affected factors. Methods: From October 2020 to April 2021, using a random sampling method, 1197 workers exposed to noise in petrochemical factories, textile factories, and parts manufacturing factories were selected as the study subjects. The noise reduction effect of hearing protectors worn by workers in daily use was tested using a hearing protector suitability testing system. The personal sound attenuation level (PAR) was compared among workers in three enterprises, Targeted intervention and repetitive testing were conducted for workers who did not meet the noise reduction effect required by the enterprise, and the changes in PAR of workers before and after the intervention were compared. The comparison of baseline PARs between two or more groups was performed using the Mann Whitney test, the comparison of baseline PARs with post intervention PARs was performed using the Wilcoxon signed rank sum test, and the comparison of qualitative data between two or more groups was performed using the Chi square test. Results: The median baseline PAR for all workers was 15 dB. Men, age<30 years old, education level at or above college level, working experience of 5 to 15 years, and those who used hearing protectors for 5 to 15 years had higher PARs, with statistically significant differences (P<0.05). The median difference in baseline PAR among workers from three enterprises was statistically significant (H=175.06, P<0.01). The median PAR of subjects who did not pass the baseline increased from 3 dB to 21 dB after intervention (Z=-27.92, P<0.01) . Conclusion: Some workers wearing hearing protectors do not meet the required PAR, and low PARs may be related to incorrect wearing methods and incorrect selection of hearing protectors. As a tool for testing, training, and assisting in selection, the hearing protector suitability testing system is of great significance for worker hearing protection.

[Characteristics of autonomic neuropathy in patients with vestibular migraine].

Objective: To investigate the characteristics of autonomic neuropathy in patients with vestibular migraine (VM) by sympathetic skin reflex (SSR) and R-R interval variation (RRIV). Methods: Seventy-three patients with interseizure VM and 36 healthy controls in the Department of Neurology affiliated to Shanghai Fourth People's Hospital of Tongji University from November 1, 2019 to December 31, 2021 were prospectively enrolled. SSR and RRIV were performed and relevant parameters were recorded, including SSR latency, SSR amplitude, RRIV during calm breathing (R%), RRIV during deep breathing (D%), RRIV difference between deep breathing and calm breathing (D%-R%), RRIV ratio between deep breathing and calm breathing (D%/R%), and the difference and correlation of various parameters between VM patients and healthy controls were analyzed. Results: Among the 73 patients with VM, there were 12 males and 61 females, and aged (46±13) years. While among 36 healthy controls, there were 6 males and 30 females, and aged (46±7) years. Among the 73 VM patients, abnormal SSR, abnormal RRIV, abnormal SSR and RRIV, and abnormal SSR or RRIV was detected in 38 cases (52%), 17 cases (23%), 11 cases (15%) and 44 cases (60%), respectively. Compared with healthy controls, the lower extremity SSR latency [(1 719±289) ms] in VM patients was longer than that in control group [(1 500±349) ms] (P=0.001), but the upper extremity SSR amplitude [1.6 (0.8, 3.0) mV] was lower than that in control group [2.6 (1.8, 4.2) mV] (P=0.006). SSR amplitude, R% and D% were negatively correlated with age in VM patients (rs=-0.311, P=0.007; rs=-0.237, P=0.043; rs=-0.263, P=0.024, respectively). SSR of lower extremity in VM patients was longer than that of upper extremity [(1 719±289) ms vs (1 244±185) ms, P<0.001], but the amplitude of lower extremity was lower than that of upper extremity [0.8 (0.3, 1.7) mV vs 1.6 (0.8, 3.0) mV, P<0.001]. SSR latency of upper limb was positively correlated with SSR latency of lower limb (r=0.436, P<0.001), the amplitude of upper limb was positively correlated with amplitude of lower limb (rs=0.456, P<0.001), and D% was positively correlated with R% (rs=0.357, P=0.002). Conclusion: The autonomic neuropathy during VM interphase features with imbalance between sympathetic and parasympathetic nervous system, and the sympathetic nerve function is mainly impaired.

Top 100 Highly Cited Articles on Rhinoplasty between 2001 and 2020: A Bibliometric and Visualized Analysis.

BACKGROUND: The authors performed a bibliometric and visualized analysis of the top 100 highly cited articles in rhinoplasty published between 2001 and 2020, to provide researchers with the present research status and the potential directions. METHODS: The authors obtained data from the Web of Science Core Collection on April 7, 2021. Quantitative and qualitative analyses were performed using the Web of Science. Collaboration and keyword analyses were performed using VOSviewer software. RESULTS: The top 100 highly cited articles included 86 original research articles and 14 reviews. The average total citations was 77 (range, 50 to 202). The article with 202 citations was published by Toriumi in 2006 and was the most influential reference. The most common level of evidence was level IV ( n = 24). Only five articles had a level of evidence of I. The top 100 articles were published in 24 journals. Plastic and Reconstructive Surgery published 49 articles with 4013 citations. The United States published the most highly cited articles. The University of Texas System published 16 articles with 1166 citations. R. J. Rohrich published 14 articles with 1025 total citations. "Cleft lip and palate," "FACE-Q," "Functional Rhinoplasty Outcome Inventory 17," "NOSE scale" (Nasal Obstruction Symptom Evaluation scale), "quality-of-life," "questionnaire," and "RHINO scale" (Rhinoplasty Health Inventory and Nasal Outcomes scale) were important keywords. CONCLUSIONS: Plastic and Reconstructive Surgery was the most influential journal, most research was reported from the United States, and the University of Texas System published the most highly cited article. R. J. Rohrich, R. K. Daniel, and B. Guyuron were the most prolific and influential authors. Global cooperation in rhinoplasty requires further strengthening.

[Inter-laboratory comparison analysis of noise measurement in 91 occupational hygiene technical service organizations].

Objective: To understand the comparability of noise measurement results of various occupational hygiene technical service organizations in Guangdong Province by conducting inter-laboratory comparison of measuring instruments and personnel operation. Methods: In October 2020, the instrument comparison and personnel comparison among 91 occupational hygiene technical service organizations engaged in noise measurement in Guangdong Province were carried out in the form of fixed-point measurement and simulated workplace measurement, and the results were analyzed and evaluated by using the robust z-ratio score. Results: In the instrument comparison, 6 organizations had 1 or 2 outliers in their z-ratio scores, 2 organizations had 2 problematic values in their z-ratio scores, and a total of 8 organizations (accounting for 8.8%) were judged as unqualified; A total of 83 organizations (accounting for 91.2%) with satisfactory z-ratio scores or only one problematic value were judged as qualified. In the personnel comparison, there were 11 organizations with 1 or 2 outliers in the z-ratio score, and 1 organization with 2 problematic values in the z-ratio score. A total of 12 organizations (13.2%) were judged as unqualified and 79 organizations (accounting for 86.8%) with satisfactory z-ratio scores or only one problematic value were judged as qualified. Through comprehensive judgment, 20 organizations (22.0%) were judged as unqualified, and 71 organizations (78.0%) were judged as qualified. There was no statistically significant difference in the qualified rates of instrument comparison results, personnel comparison results and comprehensive evaluation results of non-private organizations and private organizations (P>0.05). There was no significant difference in the qualified rates of instrument comparison results and comprehensive evaluation results of qualified organizations and unqualified organizations (P>0.05), there was significant difference in the qualified rate of personnel comparison results (P<0.05) . Conclusion: The noise measurement results of some occupational health technical service organizations in Guangdong Province are generally comparable. To carry out inter-laboratory comparison of noise instrument performance and personnel operation ability of occupational hygiene technical service organizations, can comprehensively evaluate the testing process of each organization and find out the problems existing in each organization.

[CBL inhibits proliferation and invasion of breast cancer cells by ubiquitylation-mediated degradation of NCK2].

OBJECTIVE: To observe the effects of Casitas B lymphoma (CBL) protein on proliferation, migration and invasion of breast cancer cells and explore its mechanism of action. METHODS: Cultured breast cancer cell lines MDA-MB-231 and MCF7A were transfected with a CBL-overexpressing plasmid and a specific siRNA targeting CBL (siRNA-CBL), respectively, and the changes in cell proliferation, migration and invasion were examined using colony-forming assay, cell counting kit-8 (CCK-8), scratch test and Transwell assay. Flow cytometry and Western blotting were performed to examine the effects of CBL overexpression on cell cycle and epithelial-mesenchymal transition (EMT) of MDA-MB-231 cells, and the changes in the number of filamentous pseudopodia were observed by rhodamine- labeled phalloidin staining of the cytoskeleton. IP-mass spectrometry identified NCK2 as the interacting proteins of CBL, and their interaction was verified by immunoprecipitation and immunofluorescence co-localization experiments in HEK-293T cells transfected with the plasmids for overexpression of CBL, NCK2, or both. Cycloheximide tracking and ubiquitination assays were used for assessing the effects of CBL on stability and ubiquitination of NCK2 protein in MDA-MB-231 cells; CCK-8 and Transwell assays were used to determine the effect of NCK2 overexpression on CBL-mediated proliferation and migration of the cells. RESULTS: The proliferation, migration and invasion were significantly suppressed in MDA-MB-231 cells overexpressing CBL (P < 0.05) and significantly enhanced in MCF7 cells with CBL silencing (P < 0.01). Silencing of CBL promoted G1/S transition in MCF7 cells (P < 0.05). Overexpression of CBL significantly decreased the expressions of CDK2/4 (P < 0.01), cyclinA2/B1/D1/D3/E2 (P < 0.05), Snail, N-cadherin, claudin-1 (P < 0.05), and upregulated the expression of E-cadherin (P < 0.05). CBL silencing upregulated the expressions of CDK2/4/6 (P < 0.05), cyclin A2/B1/D1/D3/E2 (P < 0.05), Snail, vimentin, and claudin-1 (P < 0.05) and down-regulated E-cadherin expression (P < 0.05). CBL overexpression obviously reduced the number of filamentous pseudopodia in MDA-MB-231 cells, and the reverse changes were observed in MCF7 cells with CBL silencing. In MDA-MB-231 cells, CBL overexpression lowered NCK2 protein stability (P < 0.05) and promoted its ubiquitin-mediated degradation (P < 0.01). Overexpression of NCK2 obviously reversed CBL-mediated inhibition of cell proliferation and migration (P < 0.01). CONCLUSION: CBL can inhibit the proliferation, migration and invasion of breast cancer cells through ubiquitination-mediated degradation of NCK2.

[Clinical and StAR genetic characteristics of 33 children with congenital lipoid adrenal hyperplasia].

Objective: To analyze the clinical and genetic characteristics of 33 children with congenital lipoid adrenal hyperplasia (CLAH) caused by StAR gene defects. Methods: The clinical, biochemical, genetic, and follow-up (until December 2021) data of 33 children diagnosed with CLAH from 2006 to 2021 were retrospectively analyzed in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Results: Of the 33 children with CLAH, 17 had a karyotype of 46, XX and 16 had a karyotype of 46, XY; 31 were female and 2 were male by social gender. Classic type and non-classic type were found in 30 and 3 children respectively. The age at diagnosis was 9.0 (3.0, 34.5) months. All the 30 cases with classic CLAH presented within the first year of life with skin hyperpigmentation (28 cases, 93%), vomiting and(or) diarrhea (19 cases, 63%), no increase in body weight (8 cases, 27%), elevated adrenocorticotropic hormone levels (21cases (70%)>275 pmol/L), decreased cortisol levels (47 (31,126) nmol/L), hyponatremia ((126±13) mmol/L), hyperkalemia ((5.7±1.1) mmol/L), and normal 17α-hydroxyprogesterone levels (30 cases, 100%). All these with classic CLAH exhibited female external genitalia. Three children with non-classic CLAH (including 2 cases of 46, XY and 1 case of 46, XX) also showed signs and symptoms of adrenal insufficiency, but 2 of them had an age of onset later than 1 year of age, including 1 case of 46, XY with male external genitalia and 1 case of 46, XX with female external genitalia. The other 46, XY patient with non-classic CLAH presented with adrenal insufficiency at 2 months of age, showing micropenis and hypospadias. In the 17 females with 46, XX, 4 older than 10 years of age showed spontaneous pubertal development. A total of 25 StAR gene pathogenic variants were identified in 33 patients, with p.Q258* (18/66, 27%), p.K236Tfs*47 (8/66, 12%) and p.Q77* (6/66, 9%) being the common variantion. Six novel variants were found, including c.358T>G, c.713_714del, c.125del, c.745-1G>A, c.179-2A>C, and exon 1 deletion. Conclusions: Patients with classic CLAH typically present with signs and symptoms of primary adrenal insufficiency in the early infancy period and female external genitalia. p.Q258*, p.K236Tfs*47 and p.Q77* are common variants in CLAH patients.

[Effects of cinepazide maleate injection on blood pressure in patients with acute ischemic stroke and hypertension].

Objective: To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection. Methods: This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes. Results: This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%,P>0.05) between cinepazide maleate group and control group. Conclusion: Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

[Multicenter real-world study on safety and efficacy of neoadjuvant therapy in combination with immunotherapy for colorectal cancer].

Objective: To provide reference and evidence for clinical application of neoadjuvant immunotherapy in patients with colorectal cancer through multicenter large-scale analysis based on real-world data in China. Methods: This was a retrospective multicenter case series study. From January 2017 to October 2021, data of 94 patients with colorectal cancer who received neoadjuvant immunotherapy in Peking University Cancer Hospital (55 cases), Union Hospital of Tongji Medical College of Huazhong University of Science and Technology (19 cases), Sun Yat-sen University Cancer Center (13 cases) and Changhai Hospital of Navy Medical University (7 cases) were retrospectively collected, including 48 males and 46 females. The median age was 58 years. Eighty-one cases were rectal cancer and 13 cases were colon cancer (2 cases of double primary colon cancer). Twelve cases were TNM staging II and 82 cases were stage III. Forty-six cases were well differentiated, 37 cases were moderately differentiated and 11 cases were poorly differentiated. Twenty-six patients (27.7%) with mismatch repair defects (dMMR) and microsatellite instability (MSI-H) were treated with immunotherapy alone, mainly programmed cell death protein-1 (PD-1); sixty-eight cases (72.3%) with mismatch repair proficient (pMMR) and microsatellite stability (MSS) were treated with immune combined with neoadjuvant therapy, mainly CapeOx (capecitabine+oxaliplatin) combined with PD-1 antibody plus long- or short-course radiotherapy, or PD-1 antibody combined with cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody. Analysis and evaluation of adverse events during neoadjuvant immunotherapy were performed according to the National Cancer Institute Common Toxicity Standard version 3.0; the surgical complications were evaluated according to the Clavien-Dindo grading standard; the efficacy evaluation of neoadjuvant immunotherapy included the following indicators: major pathological remission (MPR) was defined as tumor regression induced by neoadjuvant therapy in pathology residual tumor ≤10%; pathological complete response (pCR) was defined as tumor regression induced by neoadjuvant therapy without residual tumor in pathology; the tumor response rate was disease control rate (DCR), namely the proportion of complete response (CR), partial response (PR) and stable disease (SD) in the whole group; the objective response rate (ORR) was CR+PR. Results: The median cycle of neoadjuvant immunotherapy was 4 (1-10) in whole group, and the incidence of immune-related adverse reactions was 37.2% (35/94), including 35 cases (37.2%) of skin-related adverse reactions, 21 cases (22.3%) of thyroid dysfunction and 8 cases (8.5%) of immune enteritis, of which grade III or above accounted for 1.1%. The median interval between completion of neoadjuvant therapy and surgery was 30 (21-55) days. There were 81 cases of radical resection of rectal cancer, 11 cases of radical resection of colon cancer, and 2 cases of colon cancer combined with other organ resection. The primary tumor resection of all the patients reached R0. The incidence of surgical-related complications was 22.3% (21/94), mainly anastomotic leakage (4 cases), pelvic infection (4 cases), abdominal effusion (3 cases), anastomotic stenosis (3 cases ) and abdominal and pelvic hemorrhage (2 cases). Grade I-II complications developed in 13 cases (13.8%), grade III and above complications developed in 8 cases (8.5%), no grade IV or above complications were found. During a median follow-up of 32 (1-46 ) months, DCR was 98.9% (93/94), ORR was 88.3 % (83/94), pCR was 41.5% (39/94), MPR was 60.6% (57/94). The pCR rate of 26 patients with dMMR and MSI-H undergoing simple immunotherapy was 57.7% (15/26), and MPR rate was 65.4% (17/26). The pCR rate of 68 pMMR and MSS patients undergoing combined immunotherapy was 35.3%(24/68), and MPR rate was 58.8% (40/68). Conclusions: Neoadjuvant immunotherapy has favorable tumor control rate and pathological remission rate for patients with initial resectable colorectal cancer. The incidences of perioperative adverse reactions and surgical complications are acceptable.

[Prospects and reflections on the research and development of next-generation malaria vaccines].

Vaccination is one of the most effective intervention for the containment and elimination of infectious diseases. Recently, the world's first malaria vaccine RTS, S/AS01 was approved by WHO for use among children living in moderately and highly malaria endemic areas of Africa, which brings a hope for the research and development of malaria vaccines. Here, we review the current status of malaria vaccines development and provide a perspective on the development of next-generation malaria vaccines, so as to provide insights into the successful development of malaria vaccines.

Exogenous citric acid enhances drought tolerance in tobacco (Nicotiana tabacum).

Organic acids play a pivotal role in improving plant response to long-term drought stress. External application of organic acids has been reported to improve drought resistance in several species. However, whether organic acids have similar effects in tobacco remains unknown. A screening study of the protective function of organic acids in tobacco and understanding the underlying molecular mechanism would be useful in developing a strategy for drought tolerance. Several physiological and molecular adaptations to drought including abscisic acid, stomatal closure, reactive oxygen species homeostasis, amino acid accumulation, and drought-responsive gene expression were observed by exogenous citric acid in tobacco plants. Exogenous application of 50 mm citric acid to tobacco plants resulted in higher chlorophyll content, net photosynthesis, relative water content, abscisic acid content and lower stomatal conductance, transpiration and water loss under drought conditions. Moreover, reactive oxygen species homeostasis was better maintained through increasing activity of antioxidant enzymes and decreasing hydrogen peroxide content after citric acid pretreatment under drought. Amino acids involved in the TCA cycle accumulated after external application of citric acid under drought stress. Furthermore, several drought stress-responsive genes also dramatically changed after application of citric acid. These data support the idea that external application of citric acid enhances drought resistance by affecting physiological and molecular regulation in tobacco. This study provides clear insights into mechanistic details of regulation of amino acid and stress-responsive gene expression by citric acid in tobacco in response to drought, which is promising for minimizing growth inhibition in agricultural fields.

[Risk assessment on noise-induced hearing loss of 488 workers in a petrochemical plant].

Objective: To assess the risk of noise-induced hearing loss in workers from a petrochemical plant. Methods: In October 2020, 488 male workers exposed to noise in a petrochemical plant in Guangdong Province were selected by cluster sampling. Acoustics-Estimation of Noise-Induced Hearing Loss (ISO 1999: 2013) was used to assess the risk of noise-induced hearing loss of workers, and individual fit testing was used to evaluate the sound attenuation obtained by the workers. The risk assessment results and fitness test results of workers with different hearing levels were compared. Results: The average noise exposure equivalent sound level of the workers in the petrochemical plant was 86.7 dB (A) . The median of PARs (personal attenuation ratings) was 16 (4, 23) dB. There were statistically significant differences in age and service years among workers with different hearing results (P<0.05) , but no statistically significant differences in noise intensity and PARs (P>0.05) . According to risk assessment results of ISO 1999: 2013, the current risk of high-frequency hearing loss in 488 workers were negligible risk and acceptable risk. The risk of noise-induced deafness weredivided into three levels: negligible risk in 452 workers (92.7%) , medium risk in 27 workers (5.5%) and high risk in 9 workers (1.8%) . The risk of high-frequency hearing loss in next 5 to 15 years for workers with noise exposure level of >94 to 97 dB and >97 dB or above would be medium risk or above. The risk of noise-induced deafness in next 5 to 15 years for workers exposed to noise withlevel of 91 to 94 dB would be medium risk or above. Conclusion: The risk of noise-induced hearing loss in workers from the petrochemical plant is high in next 5 to 15 years, and noise prevention and control measures need to be strengthened. ISO1999: 2013 assessment method may underestimate the risk of hearing loss among workers.

[Effects of melatonin on PBDE-47-induced abnormal autophagy and apoptosis in PC12 cells].

OBJECTIVE: To explore the effect of melatonin (MT) on 2, 2', 4, 4'-tetrabromodiphenylether (PBDE-47)-induced abnormal autophagy and apoptosis in rat adrenal medullary pheochromocytoma PC12 cells. METHODS: PC12 cells were pretreated with a concentration gradient (12.5, 25, 50, 100, and 200 µmol/L) of melatonin for 2 h before exposure to 20 µmol/L PBDE-47 for 24 h to determine the optimal concentration of melatonin for cell treatment. In subsequent experiments, PC12 cells were treated with 0.5‰ DMSO (control group), 20 µmol/L PBDE-47, 25 µmol/L melatonin, or both PBDE-47 and melatonin. Immunofluorescence assay was used to detect the positive staining of microtubule associated protein 1 light chain 3 (LC3; a marker protein of autophagy); Western blotting was performed to determine the expression levels of the key autophagic proteins including autophagy-related protein 7 (ATG7), LC3-Ⅱ and autophagy substrate p62, and the key apoptotic proteins including active cysteine-containing aspartate specific protease-3 (active caspase-3) and cleaved poly(ADP ribose) polymerase (cleaved PARP). RESULTS: PBDE-47 treatment significantly reduced the viability of PC12 cells (P=0.001), but pretreatment with 25 µmol/L melatonin maintained a cell viability over 80% following exposure to PBDE-47 (P=0.023). PBDE-47-treated PC12 cells showed obviously enhanced immunofluorescent staining of LC3 protein, a significantly decreased expression of ATG7 and increased expression levels of p62, LC3-Ⅱ, active caspase-3 and cleaved PARP (P < 0.001). The cells treated with both PBDE-47 and melatonin showed obviously reduced staining of LC3 protein with a signficantly increased expression level of ATG7 (P=0.034) and decreased expressions of p62 (P=0.048), LC3-Ⅱ (P=0.018), active caspase-3 (P < 0.001) and cleaved PARP (P=0.032). CONCLUSION: PBDE-47 exposure impairs autophagy to cause autophagosome accumulation and promote apoptosis of PC12 cells. Melatonin can improve PBDE-47-induced abnormal autophagy and apoptosis and thus promote the survival of PC12 cells.

Room temperature mid-infrared fiber lasing beyond 5 µm in chalcogenide glass small-core step index fiber.

This Letter, to the best of our knowledge, reports mid-infrared fiber lasing beyond 5 µm at room temperature for the first time, Ce3+-doped, chalcogenide glass, step index fiber employed in-band pumping with a 4.15 µm quantum cascade laser. The lasing fiber is was 64 mm long, with a calculated numerical aperture of 0.48 at the lasing wavelengths. The core glass was Ge15As21Ga1Se63 atomic % (at. %), doped with 500 parts-per-million-by-weight Ce, with a 9 µm core diameter. The cladding glass was Ge21Sb10Se69 at. % with a 190 µm outer diameter. As pump power increases continuous wave lasing corresponding to the 2F7/2→2F5/2, transition in the Ce3+ ion occurs at 5.14 µm, 5.17 µm, and 5.28 µm.

[Study on the expression of microRNA-1825 in serum of pre-operative and post-operative patients with breast cancer].

By measuring the relative expression level of miR-1825 in serum of pre-operative and post-operative patients with breast cancer and healthy subjects, the clincal value of miR-1825 for pre-operative and post-operative breast cancer patients was evaluated.The serum of pre-operative breast cancer patients(n=92), post-operative breast cancer patients(n=64) and healthy subjects(n=60) were collected from General Hospital of Southern Theatre Command of PLA from October 2018 to March 2021. Real-time quantitative PCR was used to detect the relative expression of miR-1825 in the serum of breast cancer patients and healthy controls. The clinicopathological data were used to analyze the correlation between the expression level of miR-1825 and serum tumor markers level. The receiver operating characteristic curve (ROC) was used to evaluate the diagnosis value of breast cancer with miR-1825, CA15-3. Mann-Whitney U test was used for comparisons between two groups,and Kruskal-Wallis H test was used for multiple group comparisons. The correlation between miR-1825 and CEA, CA15-3, CA-125 expression were analyzed using Spearman correlation test.The relative expression level of miR-1825 in serum of pre-operative patients with breast cancer 1.290(0.705, 1.793) was significantly higher than that of healthy controls 0.18(-0.876, 0.725), but decreased after surgery and chemotherapy -0.080(-0474, 0.405). The analysis of clinicopathological characteristics found that the expression level of miR-1825 was higher in patients with stage Ⅲ-Ⅳ, low degree of tissue differentiation, and tumor larger than 2 cm[stageⅠ-Ⅱ:0.975(0.458, 1.380), stageⅢ-Ⅳ: 1.955(1.663, 2.535), U=98.000, P<0.001;low degree of tissue differentiation:1.685(1.448, 2.143), high/medium degree of tissue differentiation:0.700(0.395, 0.898), U=15.500, P<0.001; tumor smaller than 2 cm:0.935(0.438, 1.370), tumor larger than 2 cm:1.915(1.580, 2.288), U=215.500, P<0.001].Spearman analysis result showed that the expression of serum miR-1825 in breast cancer patients was linearly correlated with the expression of CEA (r=0.274, P=0.008) and CA15-3 (r=0.587, P<0.001); ROC curve result showed that miR-1825 was able to distinguish preoperative breast cancer patients from healthy people and postoperative patients. When using one biomarker to discriminate pre-operation and post-operation patients,miR-1825 had the best diagnostic efficiency,with an area under the ROC curve(AUC) of 0.914(95%CI: 0.872-0.956). miR-1825 may become a potential serum marker for the diagnosis of breast cancer and monitoring of therapeutic efficacy.

[Analysis on job burnout status and its influencing factors among female workers of labor-intensive enterprises].

Objective: To analyze the status and its influencing factors of job burnout among female workers of labor-intensive enterprises. Methods: A total of 750 female workers from 5 labor-intensive enterprises in Guangdong Province were selected as the study subjects by random cluster sampling method in August, 2019. 665 valid questionnaires were collected, and the effective recovery rate was 88.67%. The Maslach Burnout Inventory-General Survey was used to assess job burnout and its influencing factors were analyzed. Results: Among 665 female workers, 429 (64.51%) found to have different levels of burnout, among which 380 (57.14%) were mild to moderate burnout and 49 (7.37%) were severe burnout. The comprehensive scores of job burnout in different age, marital status, current post working age, working time per week, personal monthly income, working system and occupational stress groups were statistically significant (P<0.01) . There were significant differences in the score of emotional exhaustion in different age, marital status, current working age, working time per week, personal monthly income and occupational stress groups (P<0.05) . There were significant differences in the dimensions of depersonalization in different age, weekly work time, personal monthly income, working system and occupational stress groups (P<0.05) . There were significant differences in the dimensions of low individual achievement in different education levels, weekly work time, working system and occupational stress groups (P<0.05) . Conclusion: The female workers of labor-intensive enterprises are generally have mild to moderate job burnout. The main influencing factors of job burnout are weekly work time and occupational stress.

Automatic Machine Learning to Differentiate Pediatric Posterior Fossa Tumors on Routine MR Imaging.

BACKGROUND AND PURPOSE: Differentiating the types of pediatric posterior fossa tumors on routine imaging may help in preoperative evaluation and guide surgical resection planning. However, qualitative radiologic MR imaging review has limited performance. This study aimed to compare different machine learning approaches to classify pediatric posterior fossa tumors on routine MR imaging. MATERIALS AND METHODS: This retrospective study included preoperative MR imaging of 288 patients with pediatric posterior fossa tumors, including medulloblastoma (n = 111), ependymoma (n = 70), and pilocytic astrocytoma (n = 107). Radiomics features were extracted from T2-weighted images, contrast-enhanced T1-weighted images, and ADC maps. Models generated by standard manual optimization by a machine learning expert were compared with automatic machine learning via the Tree-Based Pipeline Optimization Tool for performance evaluation. RESULTS: For 3-way classification, the radiomics model by automatic machine learning with the Tree-Based Pipeline Optimization Tool achieved a test micro-averaged area under the curve of 0.91 with an accuracy of 0.83, while the most optimized model based on the feature-selection method χ2 score and the Generalized Linear Model classifier achieved a test micro-averaged area under the curve of 0.92 with an accuracy of 0.74. Tree-Based Pipeline Optimization Tool models achieved significantly higher accuracy than average qualitative expert MR imaging review (0.83 versus 0.54, P < .001). For binary classification, Tree-Based Pipeline Optimization Tool models achieved an area under the curve of 0.94 with an accuracy of 0.85 for medulloblastoma versus nonmedulloblastoma, an area under the curve of 0.84 with an accuracy of 0.80 for ependymoma versus nonependymoma, and an area under the curve of 0.94 with an accuracy of 0.88 for pilocytic astrocytoma versus non-pilocytic astrocytoma. CONCLUSIONS: Automatic machine learning based on routine MR imaging classified pediatric posterior fossa tumors with high accuracy compared with manual expert pipeline optimization and qualitative expert MR imaging review.

High-Brightness Continuous-Wave Electron Beams from Superconducting Radio-Frequency Photoemission Gun.

Continuous-wave photoinjectors operating at high accelerating gradients promise to revolutionize many areas of science and applications. They can establish the basis for a new generation of monochromatic x-ray free electron lasers, high-brightness hadron beams, or a new generation of microchip production. In this Letter we report on the record-performing superconducting rf electron gun with CsK_{2}Sb photocathode. The gun is generating high charge electron bunches (up to 10 nC/bunch) and low transverse emittances, while operating for months with a single photocathode. This achievement opens a new era in generating high-power beams with a very high average brightness.