[MAX germline mutation-associated pheochromocytoma-paraganglioma syndrome: multiple endocrine neoplasia type 5].

The individualized precision management of hereditary pheochromocytoma (PHEO) and paraganglioma (PGL) syndromes (PPGLs) based on molecular diagnosis and molecular subtype is becoming more popular. The newly discovered MAX germline mutation-associated PPGLs are autosomally dominant and rare. To raise awareness and explore the effective management of individual diagnosis and treatment, the relevant literature published between January 2011 and February was systematically reviewed. There were a total of 101 patients in the 77 families, involving all 5 exons, containing 44 types of MAX germline mutations and mostly concentrated in exons 3 and 4 (64.4%), the main mutations were nonsense mutations and missense mutations (73.2%), and some were large fragment deletions or insertions, intron variant, gene fusion mutations were relatively infrequent. Furthermore, about 10% of the patients had a paternal parent-of-origin effect. Among the 101 patients, 96 (95.0%) developed PHEO including 15 metastatic PHEO, 61 bilateral PHEO and 35 unilateral PHEO. The age of diagnosis was (31.7±10.9) years (range: 13 to 80 years). The male to female ratio was 1.2∶1. Eleven were accompanied with chest and abdominal PGL. Eight (7.9%) were accompanied by functional pituitary adenoma. And 12 (11.9%) developed other neuroendocrine tumors (NET), of which 8 were accompanied by PHEO, including 4 hyperparathyroidism, 1 gangliocytoma and neuroblastoma, 1 pancreatic NET, 1 medullary thyroid carcinoma and 1 C cell hyperplasia. Six presented concomitant non-NET, including 1 tongue squamous cell carcinoma, 1 papillary thyroid carcinoma, 1 prostate cancer, 1 renal oncocytoma, 1 breast cancer with renal oncocytoma, and 1 thoracic chondrosarcoma with multifocal adenocarcinoma of lung. The remaining 5 cases (5.0%), including 4 other NET (2 ganglioblastoma, 1 abdominal neuroblastoma and 1 pancreatic NET) and 1 asymptomatic child, did not present PHEO. The MAX germline mutation may cause a novel multiple endocrine neoplasia, which can be described as type 5. A comprehensive baseline assessment of neural crest cell-derived diseases such as PPGL, pituitary adenoma, hyperparathyroidism, and/or gangliocytoma (neuroblastoma) was recommended for all people with MAX germline mutations, and the risk of bilateral and/or metastatic PHEO should also be considered. In contrast, patients with PPGLs combined with other NET, such as functional pituitary adenoma, should undergo genetic testing and pedigree screening that includes at least the MAX gene.

Preventative strategies for low anterior resection syndrome.

BACKGROUND: A common and debilitating complication of low anterior resection for rectal cancer is low anterior resection syndrome (LARS). As a multifactorial entity, LARS is poorly understood and challenging to treat. Despite this, prevention strategies are commonly overlooked. Our aim was to review the pathophysiology of LARS and explore current evidence on the efficacy and feasibility of prophylactic techniques. METHODS: A literature review was performed between [1st January 2000 to 1st October 2023] for studies which investigated preventative interventions for LARS. Mechanisms by which LARS develop are described, followed by a review of prophylactic strategies to prevent LARS. Medline, Cochrane, and PubMed databases were searched, 189 articles screened, 8 duplicates removed and 18 studies reviewed. RESULTS: Colonic dysmotility, anal sphincter dysfunction and neorectal dysfunction all contribute to the development of LARS, with the complex mechanism of defecation interrupted by surgery. Transanal irrigation (TAI) and pelvic floor rehabilitation (PFR) have shown benefits in preventing LARS, but may be limited by patient compliance. Intraoperative nerve monitoring (IONM) and robotic-assisted surgery have shown some promise in surgically preventing LARS. Nerve stimulation and other novel strategies currently used in treatment of LARS have yet to be investigated in their roles prophylactically. CONCLUSIONS: To date, there is a limited evidence base for all preventative strategies including IONM, RAS, PFP and TAI. These strategies are limited by either access (IONM, RAS and PFP) or acceptability (PFP and TAI), which are both key to the success of any intervention. The results of ongoing trials will serve to assess acceptability, while technological advancement may improve access to some of the aforementioned strategies.

[A real-world study on the efficacy and safety analysis of paclitaxel liposome in advanced breast cancer].

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.

[CT perfusion combined with energy spectrum imaging to evaluate the short-term efficacy of bronchial arterial chemoembolization for lung cancer].

Objective: To evaluate the clinical value of dynamic volumetric CT perfusion combined with energy spectrum imaging in bronchial arterial chemoembolization (BACE) in patients with lung cancer. Methods: The data of 31 patients with lung cancer confirmed by pathology and treated with BACE in Lishui Central Hospital from January 2018 to February 2022 were retrospectively collected, including 23 men and 8 women, aged 31-84 (67) years. All patients received perfusion scans of lesion sites within 1 week before surgery and 1 month after surgery. We collected and compared the changes in preoperative and postoperative perfusion parameters such as blood flow (BF), blood volume (BV), mean through time (MTT), permeability surface (PS) and energy spectrum parameters including arterial phase CT value (CTA), venous phase CT value (CTV), arterial phase iodine concentration (ICA), venous phase of iodine concentration (ICV), arterial standardization iodine concentration (NICA), and intravenous standardized iodine concentration (NICV) to confirm the significance of these parameters in evaluating the short-term efficacy of BACE in the treatment of advanced lung cancer. Data normality was tested using the Kolmogorov-Smirnov test and normally distributed measurement data are expressed here as mean ± standard deviation; the independent-samples t-test was used for comparisons between two groups. The measurement data that were not normally distributed are expressed as median (interquartile interval) [M (Q1, Q3)], and the comparison between the two groups used the Kruskal-Wallis test. Count data are expressed as cases (%), and comparisons between groups used the χ2 test. Results: The objective response rate (ORR) and disease control rate (DCR) at 1 month after BACE were 54.8% (17/31) and 96.8% (30/31), respectively. CT perfusion parameters and energy spectrum parameters of patients before and after BACE treatment were compared. The results showed that BF, BV, MTT, ICA, ICV and NICV were significantly decreased after BACE treatment compared with before treatment, and the differences were statistically significant[58.06 (40.47,87.22) vs.23.57(10.92, 36.24) ml·min-1·100g-1,3.33(2.86,6.09) vs.2.12(1.96,3.61)ml/100g,2.70(2.19,3.88) vs.1.53 (1.12,2.25)s, 3.51 (3.11,4.14)vs.1.74 (1.26,2.50)mg/ml,2.00 (1.30,2.45) vs.1.32(0.92,1.76)mg/ml,0.51(0.42,0.57) vs.0.33(0.23,0.39)](all P<0.05). At the same time, compared with the non-remission group, the study results showed that the difference of parameters in remission group before and after BACE was more obvious, including ΔBF, ΔBV, ΔMTT, ΔPS, ΔCTA, ΔCTV, ΔICA, ΔICV, ΔNICA, ΔNICV were significantly increased, and the difference was statistically significant [36.82(32.38, 45.34) vs.9.50(-1.43, 12.34) ml·min-1·100g-1,4.46(2.52, 5.79) vs.0.22(-0.76, 4.09) ml/100g,4.22(2.25, 6.77) vs.0.43(-2.53, 1.88) s,10.07 (2.89, 13.13) vs.-2.01(-6.77, 4.28) ml·min-1·100g-1,14.22(11.88, 20.57) vs.4.18(-5.25, 6.37) HU, 34.6(14.88, 43.15) vs.11.60(0.26, 25.05) HU,0.95(0.54, 1.47) vs.0.11(0.20, 0.59) mg/ml,1.57(1.10, 2.38) vs. 0.26(-0.21, 0.63) mg/ml,0.05(0.03, 0.08) vs.-0.02(-0.04, 0.01),0.18(0.13, 0.21)vs. 0.11(-0.06, 0.16)](all P<0.05). Conclusions: CT perfusion combined with spectral imaging could effectively evaluate the changes in tumor vascular perfusion in patients with advanced lung cancer before and after BACE treatment, which has important value in judging the short-term efficacy after treatment.

[Analysis of 15 cases of trench foot in peacetime].

Trench foot was first seen in World War Ⅰ and was one of the reasons for non combat attrition. We reviewed and analyzed 15 cases of trench foot admitted from 2010 to 2021, summarized clinical treatment methods and experiences, analyzed the causes, population characteristics, treatment methods, and treatment experiences of trench foot during peacetime, strengthened attention to high-risk groups, and improved the success rate of clinical treatment.

[Effectiveness of different screening strategies for type 2 diabete on preventing cardiovascular diseases in a community-based Chinese population using a decision-analytic Markov model].

OBJECTIVE: To evaluate the effectiveness of different screening strategies for type 2 diabetes to prevent cardiovascular disease in a community-based Chinese population from economically developed areas based on the Chinese electronic health records research in Yinzhou (CHERRY) study. METHODS: A Markov model was used to simulate different systematic diabetes screening strategies, including: (1) screening among Chinese adults aged 40-70 years recommended by the 2020 Chinese Guideline for the prevention and Treatment of Type 2 Diabetes (Strategy 1); (2) screening among Chinese adults aged 35 to 70 years recommended by the 2022 American Diabetes Association Standard of Medical Care in Diabetes (Strategy 2); and (3) screening among Chinese adults aged 35-70 years with overweight or obesity recommended by the 2021 United States Preventive Services Task Force Recommendation Statement on Screening for Prediabetes and Type 2 Diabetes (Strategy 3). According to the guidelines, individuals who were screened positively (fasting plasma glucose ≥ 7.0 mmol/L) would be introduced to intensive glycemic targets management (glycated hemoglobin < 7.0%).The Markov model simulated different screening scenarios for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Number of cardiovascular disease events or deaths could be prevented and number needed to screen (NNS) were calculated to compare the effectiveness of the different strategies. One-way sensitivity analysis on the sensitivity of screening methods and probabilistic sensitivity analysis on uncertainties of diabetes incidence, the sensitivity of screening methods, and intensive glycemic management effects were conducted. RESULTS: Totally 289 245 Chinese adults aged 35-70 years without cardiovascular diseases or diagnosed diabetes at baseline were enrolled. In terms of the number of cardiovascular disease events could be prevented, Strategy 1 for systematic diabetes screening among the adults aged 35-70 years was 222 (95%UI: 180-264), Strategy 2 for systematic diabetes screening among the adults aged 40-70 years was 227 (95%UI: 185-271), and Strategy 3 for systematic diabetes screening among the adults aged 35-70 years with obesity or overweight (body mass index ≥ 24 kg/m2) was 131 (95%UI: 98-164), compared with opportunistic screening. NNS per cardiovascular disease event for the strategies 1, 2 and 3 were 1 184 (95%UI: 994-1 456), 1 274 (95%UI: 1 067-1 564) and 814 (95%UI: 649-1 091), respectively. Compared with Strategy 1, NNS per cardiovascular disease event for Strategy 2 increased by 90 (95%UI: -197-381) with similar effectiveness of cardiovascular prevention; however, NNS per cardiovascular disease event for Strategy 3 was reduced by 460 (95%UI: 185-724) in contrast to the Strategy 2, suggesting that the Strategy 3 was more efficient. The results were consistent in multiple sensitivity analyses. CONCLUSION: Systematic screening for diabetes based on the latest guidelines in economically developed areas of China can reduce cardiovascular events and deaths. However, merely lowering the starting age of screening from 40 to 35 years seems ineffective for preventing cardiovascular disease, while screening strategy for Chinese adults aged 35-70 years with overweight or obesity is recommended to improve efficiency.

[Construction of prediction model combined dual-energy CT quantitative parameters and conventional CT features for assessing the Ki-67 expression levels in invasive breast cancer].

Objective: To develop a model combined with dual-energy CT quantitative parameters and conventional CT features for evaluating the expression level of Ki-67 in invasive breast cancer. Methods: A total of 191 patients with histologically confirmed invasive breast cancer in Lishui Central Hospital from March 2019 to December 2020, were retrospectively enrolled, all of them were females, aged from 25 to 77 (53.2±11.3) years. All patients underwent preoperative non-contrast chest and contrast-enhanced Dual energy CT scans, and the normalized iodine concentration (NIC) of lesions on arterial and venous phase, spectral curve slope (λHU), and normalized effective atomic number (nZeff) were measured and calculated, and their conventional CT characteristics were assessed. According to the results of immunohistochemistry (IHC), the patients were divided into Ki-67 high expression group (n=129 patients) and low expression group (n=62 patients) level. The differences in clinical data, conventional CT characteristics and dual-energy CT quantitative parameters between the two groups were analyzed. The receiver operating characteristic curve (ROC) curve was conducted to assess the efficacy of each individual model and joint model in evaluating Ki-67 expression levels, and the area under the curve (AUC), sensitivity, specificity, and accuracy were calculated, respectively. Results: In the analysis of CT features, the longest diameter, shape and enhancement pattern of the tumor were significantly difference between the two groups (all P<0.05). The NIC, nZeff on the arterial phase and NIC, nZeff and λHU [M(Q1,Q3)] on the venous phase were higher in the high Ki-67 expression group compared to the low expression group [0.13 (0.12, 0.16) vs 0.11 (0.08, 0.14), 0.71 (0.70, 0.75) vs 0.70 (0.67, 0.72), 0.40 (0.32, 0.48) vs 0.23 (0.17, 0.32), 3.10 (2.58, 3.63) vs 2.86 (2.19, 3.48), 0.88 (0.85, 0.92) vs 0.85 (0.84, 0.86), all P<0.05]. The logistic regression model, which integrated significant conventional CT features and dual-energy CT quantitative parameters, demonstrated the highest diagnostic performance for assessing Ki-67 expression levels, with an AUC of 0.924, sensitivity of 88.37%, specificity of 83.87%, and accuracy of 86.91%; the AUC of the dual-energy CT parameter model was 0.908, sensitivity of 82.17%, specificity of 88.71%, and accuracy of 84.29%. Though the diagnostic efficacy was no significant difference (P=0.238), both models showed superior to the conventional CT feature model (all P<0.001). Conclusion: A dual-energy CT quantitative parameter combined with a conventional CT feature model was successfully constructed, which has a good evaluation performance on the expression level of Ki-67 in invasive breast cancer.

[Standardization of spirometry updated in China and international: comparison and interpretation of the key updates].

Standardization of spirometry was jointly updated by the American Thoracic Society (ATS) and the European Respiratory Society (ERS) in 2019. Similar technical standards for spirometry recommended by the Chinese Thoracic Society (CTS) and/or the Chinese Association of Chest Physicians (CACP) are widely used in China. We compared the key similarities and differences of these recommendations and interpreted the key updates. The ATS/ERS 2019 updates expanded the scope of indications for spirometry and recommended the contraindications based on the pathophysiological perspective, while contraindications recommended by the CTS were based on the severity of contraindications. ISO 26782∶2009 standards were applied by the ATS/ERS 2019 to evaluate the performance quality (reliance for accuracy, repeatability, etc.) of spirometers, while standards adopted 24/26 waves suggested by the ATS 1994 was used by the CTS. The ATS/ERS 2019 also included the performance quality control criteria for 3-L calibration syringe, operator training and attainment and maintenance of competency, grade"U", system warning messages, instructions to patients, and standardized operator comments. Some of these criteria in the CTS were not explained in detail. However, the CTS/CACP emphasized that the spirometry record should report the indices of forced inspiratory phase and small airway function, those are not clearly required in the ATS/ERS 2019. In comparison, the ATS/ERS 2019 has stricter criteria for FEV1 and FVC acceptability than the CTS and more detailed explanations. Those outstanding parts are worth referencing for the updated version of the CTS in the future, while the criteria that combine our own conditions need to be retained and popularized.

Gamma-Ray Observation of the Cygnus Region in the 100-TeV Energy Region.

We report observations of gamma-ray emissions with energies in the 100-TeV energy region from the Cygnus region in our Galaxy. Two sources are significantly detected in the directions of the Cygnus OB1 and OB2 associations. Based on their positional coincidences, we associate one with a pulsar PSR J2032+4127 and the other mainly with a pulsar wind nebula PWN G75.2+0.1, with the pulsar moving away from its original birthplace situated around the centroid of the observed gamma-ray emission. This work would stimulate further studies of particle acceleration mechanisms at these gamma-ray sources.

First Detection of sub-PeV Diffuse Gamma Rays from the Galactic Disk: Evidence for Ubiquitous Galactic Cosmic Rays beyond PeV Energies.

We report, for the first time, the long-awaited detection of diffuse gamma rays with energies between 100 TeV and 1 PeV in the Galactic disk. Particularly, all gamma rays above 398 TeV are observed apart from known TeV gamma-ray sources and compatible with expectations from the hadronic emission scenario in which gamma rays originate from the decay of π^{0}'s produced through the interaction of protons with the interstellar medium in the Galaxy. This is strong evidence that cosmic rays are accelerated beyond PeV energies in our Galaxy and spread over the Galactic disk.

[A convolutional neural network based model for assisting pathological diagnoses on thyroid liquid-based cytology].

Objective: To develop a convolutional neural network based model for assisting pathological diagnoses on thyroid liquid-based cytology specimens. Methods: Seven-hundred thyroid TCT slides were collected, scanned for whole slide imaging (WSI), and divided into training and test sets after labeling the correct diagnosis (benign versus malignant). The extracted regions of interest after noise filtering were cropped into pieces of 512 × 512 patch on 10 × and 40 × magnifications, respectively. A classification model was constructed using deeply learning algorithms, and applied to the training set, then automatically tuned in the test set. After data enhancement and parameters optimization, accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the model were calculated. Results The training set with 560 WSI contained 4 926 cell clusters (11 164 patches), while the test set with 140 WSI contained 977 cell clusters (1 402 patches). YOLO network was selected to establish a detection model, and ResNet50 was used as a classification model. With 40 epochs training, results from 10× magnifications showed an accuracy of 90.01%, sensitivity of 89.31%, specificity of 92.51%, positive predictive value of 97.70% and negative predictive value of 70.82%. The area under curve was 0.97. The average diagnostic time was less than 1 second. Although the model for data of 40× magnifications was very sensitive (98.72%), but its specificity was poor, suggesting that the model was more reliable at 10× magnification. Conclusions: The performance of a deep-learning based model is equivalent to pathologists' diagnostic performance, but its efficiency is far beyond. The model can greatly improve consistency and efficiency, and reduce the missed diagnosis rate. In the future, larger studies should have more morphology diversity, improve model's accuracy and eventually develop a model for direct clinical use.

[Application of adaptive technology-based speech recognition system in 600 pathological grossing process].

Objective: To establish a speech recognition system based on adaptive technology and to evaluate its value in pathological grossing processes. Methods: A total of 600 tissue specimens were collected at the Zhejiang Provincial People's Hospital affiliated to Hangzhou Medical College between October 1, 2020 and December 31, 2020. A speech recognition system based on adaptive technology was used in the pathological grossing processes, and the pathological examination reports were generated and extracted. Results: The speech recognition system based on adaptive technology showed a good recognition rate (overall recognition rate = 77.87%) and helped achieve rapid input and output of pathological examination data. Conclusions: The speech recognition system can reduce the labor costs, improve the work efficiency of pathologists and increase the quality of medical services, which may be valuable for building next-generation smart hospitals.

[Role of NF-κB p65 and related cytokines in rats with liver function injury induced by dibutyl phthalate and benzo (a) pyrene].

Objective: To explore the role of nuclear factor-κB (NF-κB) p65 and related cytokines in rats with liver function injury induced by dibutyl phthalate (DBP) and benzo (a) pyrene (BaP) , in order to provide support for enriching the mechanism of liver injury induced by DBP and BaP. Methods: In September to December of 2019, a total number of 160 specific pathogen free Sprague Dawley rats were numbered in order of sex and body weight, then using the statistical table of random numbers, they were randomly divided into eight groups and each group consists of twenty animals (10 male and 10 female rats) , including blank control group, vehicle control group (given corn oil) , DBP 50 mg/kg (DBP(50)) group, DBP 250 mg/kg (DBP(250)) group, BaP 1 mg/kg (BaP(1)) group, BaP 5 mg/kg (BaP(5)) group, DBP 50 mg/kg plus BaP 1 mg/kg (DBP(50)+BaP(1)) group and DBP 250 mg/kg plus BaP 5 mg/kg (DBP(250)+BaP(5)) group, then DBP and BaP were administered to rats as a homogenous mixture in corn oil by gavage. After exposure for 90 days, liver was separated to test the mRNA and protein expression levels of NF-κB p65 by Real-time fluorescence quantitative polymerase chain reaction and Western blotting. Then serum of rats was collected to detect the levels of CXCL-13, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) by Enzyme-Linked Immunosorbent Assay, and the levels of alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , albumin (ALB) and total protein (TP) were detected by Reitman-Frankel assay. Results: The protein expression of NF-κB p65 in BaP(1) group was not statistically significant, but the mRNA and protein expression levels of NF-κB p65 in the liver tissues of rats in other exposure group were higher than those in the blank control group (P<0.05) , and the expression levels of NF-κB p65 increased more obvious in the DBP and BaP co-exposed groups than those in the low and high dose groups that single-exposed to DBP and BaP (P<0.05) . The serum levels of CXCL-13 and IL-6 of rats in other group were obviously higher than those of the blank control group except for the BaP(1) group, and the increase was more obvious in the high-dose group that co-exposed to DBP and BaP (P<0.05) . While the level of TNF-α in each exposure group was higher than those in the blank control group and the levels of TNF-α in the DBP and BaP co-exposed groups were strongly augmented compared to those in the low and high dose groups that single-exposed to DBP and BaP (P<0.05) . What's more, compared with the blank control group, the level of ALT in each exposure group was increased significantly. Except for the BaP(1) group, the levels of AST in other exposed groups were increased (P<0.05) , and the levels of ALT and AST in the DBP and BaP co-exposed groups were significantly elevated in comparison to the low and high dose groups that single-exposed to DBP and BaP (P<0.05) . On the contrary, the level of ALB in each exposure group was significantly lower than that in the blank control group, especially decreased significantly in the DBP and BaP co-exposed group (P<0.05) . The level of TP decreased only in the high-dose group that single and co-exposed to DBP and BaP, and the decrease was more significant in the DBP and BaP co-exposed group (P<0.05) . When DBP exposed alone, Pearson correlation analysis showed that NF-κB p65 protein expression level was positively correlated with IL-6, TNF-α and ALT (r=0.762, 0.951, and 0.924, P<0.05) . After BaP exposed alone, the NF-κB p65 protein expression level was positively correlated with TNF-α and ALT (r=0.911 and 0.910, P<0.05) . When DBP and BaP exposed together, NF-κB p65 protein expression level was positively correlated with CXCL-13, IL-6, TNF-α, ALT and AST (r=0.711, 0.764, 0.955, 0.903 and 0.827, P<0.05) . In addition, Pearson correlation analysis showed a positive correlation between TNF-α and ALT (r=0.833 and 0.894, P<0.05) when DBP or BaP exposed alone. Furthermore, when DBP and BaP exposed together, CXCL-13, IL-6 and TNF-α were positively correlated with ALT (r= 0.871, 0.925 and 0.942, P<0.05) , and also positively correlated with AST (r=0.910, 0.892 and 0.890, P<0.05) . Conclusion: Single and co-exposed to DBP and BaP may regulate the abnormal secretion of related cytokines by upregulating the expression level of NF-κB p65 in rat liver tissue, thus leading to hepatocyte injury in rats, and the damage effect may be enhanced when DBP and BaP are exposed together.

Oxidative DNA damage is concurrently repaired by base excision repair (BER) and apyrimidinic endonuclease 1 (APE1)-initiated nonhomologous end joining (NHEJ) in cortical neurons.

AIMS: Accumulating studies have suggested that base excision repair (BER) is the major repair pathway of oxidative DNA damage in neurons, and neurons are deficient in other DNA repair pathways, including nucleotide excision repair and homologous recombination repair. However, some studies have demonstrated that neurons could efficiently repair glutamate- and menadione-induced double-strand breaks (DSBs), suggesting that the DSB repair mechanisms might be implicated in neuronal health. In this study, we hypothesized that BER and nonhomologous end joining (NHEJ) work together to repair oxidative DNA damage in neurons. METHODS: Immunohistochemistry and confocal microscopy were employed to examine the colocalization of apyrimidinic endonuclease 1 (APE1), histone variant 2AX (γH2AX) and phosphorylated p53-binding protein (53BP1). APE1 inhibitor and shRNA were respectively applied to suppress APE1 activity and protein expression to determine the correlation of APE1 and DSB formation. The neutral comet assay was used to determine and quantitate the formation of DSB. RESULTS: Both γH2AX and 53BP1 were upregulated and colocalized with APE1 in the nuclei of rat cortical neurons subjected to menadione-induced oxidative insults. Phospho53BP1 foci were efficiently abolished, but γH2AX foci persisted following the suppression of APE1 activity. Comet assays demonstrated that the inhibition of APE1 decreased the DSB formation. CONCLUSIONS: Our results indicate that APE1 can engage the NHEJ mechanism in the repair of oxidative DNA damage in neurons. These findings provide insights into the mechanisms underlying the efficient repair of oxidative DNA damage in neurons despite the high oxidative burden.

First Detection of Photons with Energy beyond 100 TeV from an Astrophysical Source.

We report on the highest energy photons from the Crab Nebula observed by the Tibet air shower array with the underground water-Cherenkov-type muon detector array. Based on the criterion of a muon number measured in an air shower, we successfully suppress 99.92% of the cosmic-ray background events with energies E>100 TeV. As a result, we observed 24 photonlike events with E>100 TeV against 5.5 background events, which corresponds to a 5.6σ statistical significance. This is the first detection of photons with E>100 TeV from an astrophysical source.

[Analysis of oral sexual behavior and related factors among male students from college graduation in Hangzhou].

Objective: To study oral sexual behavior and related factors among male students. Methods: The male students from college graduation in Hangzhou were selected as the study objects, and the inclusion criteria were having had sex and informed the type of behavior. A total of 490 subjects were finally included. Results: Among 490 male students, the 20-22 years old, 23 years old and 24-27 years old age groups accounted for 38.8% (n=190), 37.8% (n=185) and 23.3% (n=114), respectively. A total of 99 (20.2%) cases had oral sexual behavior, of which only 14 (2.9%) cases used condom. After adjusting for unplanned pregnancy, stage of sexual behavior, sexually transmitted diseases infection possibility, sexual orientation factors, normal/unnormal family relationship, more than 2 sexual partners, casual sexual partners, sexual partners from other college, sexual partners from society, sexual behavior in past 1 year were positively associated with oral sexual behavior. The corresponding OR (95%CI) values were 2.77 (1.40-5.50), 2.29 (1.27-4.15), 2.68 (1.23-5.88), 2.45 (1.34-4.48), 2.47 (1.15-5.33) and 2.04 (1.05-3.96), respectively. Use of condoms was negatively associated with oral sexual behavior, the OR (95%CI) value was 0.20 (0.09-0.42). Conclusion: Normal/unnormal family relationship, more than two sexual partners, casual sexual partners, sexual partners from other college, sexual partners from society, sexual behavior in last one year and condom use in each vaginal sexual behavior were associated with oral sexual behavior.

Evaluation of the Interplanetary Magnetic Field Strength Using the Cosmic-Ray Shadow of the Sun.

We analyze the Sun's shadow observed with the Tibet-III air shower array and find that the shadow's center deviates northward (southward) from the optical solar disk center in the "away" ("toward") interplanetary magnetic field (IMF) sector. By comparing with numerical simulations based on the solar magnetic field model, we find that the average IMF strength in the away (toward) sector is 1.54±0.21_{stat}±0.20_{syst} (1.62±0.15_{stat}±0.22_{syst}) times larger than the model prediction. These demonstrate that the observed Sun's shadow is a useful tool for the quantitative evaluation of the average solar magnetic field.

Simvastatin Attenuates Neuropathic Pain by Inhibiting the RhoA/LIMK/Cofilin Pathway.

Neuropathic pain occurs due to deleterious changes in the nervous system caused by a lesion or dysfunction. Currently, neuropathic pain management is unsatisfactory and remains a challenge in clinical practice. Studies have suggested that actin cytoskeleton remodeling may be associated with neural plasticity and may involve a nociceptive mechanism. Here, we found that the RhoA/LIM kinase (LIMK)/cofilin pathway, which regulates actin dynamics, was activated after chronic constriction injury (CCI) of the sciatic nerve. Treatments that reduced RhoA/LIMK/cofilin pathway activity, including simvastatin, the Rho kinase inhibitor Y-27632, and the synthetic peptide Tat-S3, attenuated actin filament disruption in the dorsal root ganglion and CCI-induced neuropathic pain. Over-activation of the cytoskeleton caused by RhoA/LIMK/cofilin pathway activation may produce a scaffold for the trafficking of nociceptive signaling factors, leading to chronic neuropathic pain. Here, we found that simvastatin significantly decreased the ratio of membrane/cytosolic RhoA, which was significantly increased after CCI, by inhibiting the RhoA/LIMK/cofilin pathway. This effect was highly dependent on the function of the cytoskeleton as a scaffold for signal trafficking. We conclude that simvastatin attenuated neuropathic pain in rats subjected to CCI by inhibiting actin-mediated intracellular trafficking to suppress RhoA/LIMK/cofilin pathway activity.

Assessing coughing-induced influenza droplet transmission and implications for infection risk control.

Indoor transmission of respiratory droplets bearing influenza within humans poses high risks to respiratory function deterioration and death. Therefore, we aimed to develop a framework for quantifying the influenza infection risk based on the relationships between inhaled/exhaled respiratory droplets and airborne transmission dynamics in a ventilated airspace. An experiment was conducted to measure the size distribution of influenza-containing droplets produced by coughing for a better understanding of potential influenza spread. Here we integrated influenza population transmission dynamics, a human respiratory tract model, and a control measure approach to examine the indoor environment-virus-host interactions. A probabilistic risk model was implemented to assess size-specific infection risk for potentially transmissible influenza droplets indoors. Our results found that there was a 50% probability of the basic reproduction number (R0) exceeding 1 for small-size influenza droplets of 0·3-0·4 µm, implicating a potentially high indoor infection risk to humans. However, a combination of public health interventions with enhanced ventilation could substantially contain indoor influenza infection. Moreover, the present dynamic simulation and control measure assessment provide insights into why indoor transmissible influenza droplet-induced infection is occurring not only in upper lung regions but also in the lower respiratory tract, not normally considered at infection risk.

[Features and influencing factors of self-discrimination among HIV/AIDS patients according to sex].

Objective: To investigate the features and influencing factors of self-discrimination among patients with HIV/AIDS according to sex. Methods: A total of 2 432 HIV/AIDS patients were recruited in Yunnan, Henan, Hubei, Jiangsu, Shanxi, Jilin, and Inner Mongolia provinces by a multistage stratified cluster sampling method, based on HIV epidemic and transmission modes, from May 2013 to October 2013. All participants were ≥18 years old, and we excluded those with mental disorders, hearing loss or other factors that prevented them from properly answering questions, and those who were unwilling to participate. A self-designed questionnaire was conducted to collect information about self-discrimination features and social behavior changes among HIV/AIDS patients. Differences in performance and self-discrimination features between participants of different sexes were compared using the chi-squared test. Factors influencing self-discrimination were analyzed by sex, using unconditional logistic regression. Results: Of the 2 432 cases, 78.9%(1 918 cases)were male and 21.1%(514 cases)female. The proportion of self-discrimination overall was 76.1%(1 850 cases); this proportion among female HIV/AIDS patients was 80.5%(414 cases), which was higher than that among men(74.9%, 1 436 cases)(χ2=7.17, P=0.007). Of the 11 forms of self-discrimination performance, proportions of feeling guilt, shame, and self-abasement among participants were greater than 50%. Proportions of feeling shame, inferiority, and blaming others among females were 61.3%, 59.5%, and 45.3%, respectively, which were higher than these among males(49.8%, 50.0%, 28.4%, respectively)(P<0.01). Multivariate unconditional logistic regression analysis showed that the risk of self-discrimination among those with HIV confirmatory testing time ≥1 year was higher than those with HIV confirmatory testing time <1 year(females: OR=35.67, 95%CI:17.28-73.64; males: OR=8.74, 95% CI:6.79-11.25). Compared with other occupations, the risk of self-discrimination among male farm workers was higher(OR=1.62, 95% CI:1.03-2.54). The risks of self-discrimination in males who had been infected with HIV by transmission routes of blood transfusion or blood collection(OR=2.38, 95% CI:1.31-4.30), injection drug use(OR=1.78, 95% CI:1.09-2.91), and male-to-male sexual behavior(OR=1.48, 95%CI:1.08-2.03)were higher than in males infected via heterosexual behavior. Conclusion: Female HIV/AIDS patients are more likely to engage in self-discrimination than male patients. Self-discrimination mainly takes the form of feeling remorse, shame, and inferiority. Confirmatory testing time ≥1 year, occupation as a farm work, and routes of transmission via blood transfusion or collection, injection drug use, and male-to-male sexual behavior are influencing factors of self-discrimination among male HIV/AIDS patients. Confirmatory testing time ≥1 year is the influencing factor of self-discrimination among female HIV/AIDS patients.