Ultrahigh-energy photons up to 1.4 petaelectronvolts from 12 γ-ray Galactic sources.

The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 1015 electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays1. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. 2). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane3-6, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.

Constraints on Ultraheavy Dark Matter Properties from Dwarf Spheroidal Galaxies with LHAASO Observations.

In this Letter we try to search for signals generated by ultraheavy dark matter at the Large High Altitude Air Shower Observatory (LHAASO) data. We look for possible γ rays by dark matter annihilation or decay from 16 dwarf spheroidal galaxies in the field of view of the LHAASO. Dwarf spheroidal galaxies are among the most promising targets for indirect detection of dark matter that have low fluxes of astrophysical γ-ray background while having large amount of dark matter. By analyzing more than 700 days of observational data at LHAASO, no significant dark matter signal from 1 TeV to 1 EeV is detected. Accordingly we derive the most stringent constraints on the ultraheavy dark matter annihilation cross section up to EeV. The constraints on the lifetime of dark matter in decay mode are also derived.

Stringent Tests of Lorentz Invariance Violation from LHAASO Observations of GRB 221009A.

On 9 October 2022, the Large High Altitude Air Shower Observatory (LHAASO) reported the observation of the very early TeV afterglow of the brightest-of-all-time gamma-ray burst 221009A, recording the highest photon statistics in the TeV band ever obtained from a gamma-ray burst. We use this unique observation to place stringent constraints on the energy dependence of the speed of light in vacuum, a manifestation of Lorentz invariance violation (LIV) predicted by some quantum gravity (QG) theories. Our results show that the 95% confidence level lower limits on the QG energy scales are E_{QG,1}>10 times the Planck energy E_{Pl} for the linear LIV effect, and E_{QG,2}>6×10^{-8}E_{Pl} for the quadratic LIV effect. Our limits on the quadratic LIV case improve previous best bounds by factors of 5-7.

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.

Measurement of Ultra-High-Energy Diffuse Gamma-Ray Emission of the Galactic Plane from 10 TeV to 1 PeV with LHAASO-KM2A.

The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°10 TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60 TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.

Constraints on Heavy Decaying Dark Matter from 570 Days of LHAASO Observations.

The kilometer square array (KM2A) of the large high altitude air shower observatory (LHAASO) aims at surveying the northern γ-ray sky at energies above 10 TeV with unprecedented sensitivity. γ-ray observations have long been one of the most powerful tools for dark matter searches, as, e.g., high-energy γ rays could be produced by the decays of heavy dark matter particles. In this Letter, we present the first dark matter analysis with LHAASO-KM2A, using the first 340 days of data from 1/2-KM2A and 230 days of data from 3/4-KM2A. Several regions of interest are used to search for a signal and account for the residual cosmic-ray background after γ/hadron separation. We find no excess of dark matter signals, and thus place some of the strongest γ-ray constraints on the lifetime of heavy dark matter particles with mass between 10^{5} and 10^{9} GeV. Our results with LHAASO are robust, and have important implications for dark matter interpretations of the diffuse astrophysical high-energy neutrino emission.

Exploring Lorentz Invariance Violation from Ultrahigh-Energy γ Rays Observed by LHAASO.

Recently, the LHAASO Collaboration published the detection of 12 ultrahigh-energy γ-ray sources above 100 TeV, with the highest energy photon reaching 1.4 PeV. The first detection of PeV γ rays from astrophysical sources may provide a very sensitive probe of the effect of the Lorentz invariance violation (LIV), which results in decay of high-energy γ rays in the superluminal scenario and hence a sharp cutoff of the energy spectrum. Two highest energy sources are studied in this work. No signature of the existence of the LIV is found in their energy spectra, and the lower limits on the LIV energy scale are derived. Our results show that the first-order LIV energy scale should be higher than about 10^{5} times the Planck scale M_{Pl} and that the second-order LIV scale is >10^{-3}M_{Pl}. Both limits improve by at least one order of magnitude the previous results.

Extended Very-High-Energy Gamma-Ray Emission Surrounding PSR J0622+3749 Observed by LHAASO-KM2A.

We report the discovery of an extended very-high-energy (VHE) gamma-ray source around the location of the middle-aged (207.8 kyr) pulsar PSR J0622+3749 with the Large High-Altitude Air Shower Observatory (LHAASO). The source is detected with a significance of 8.2σ for E>25 TeV assuming a Gaussian template. The best-fit location is (right ascension, declination) =(95.47°±0.11°,37.92°±0.09°), and the extension is 0.40°±0.07°. The energy spectrum can be described by a power-law spectrum with an index of -2.92±0.17_{stat}±0.02_{sys}. No clear extended multiwavelength counterpart of the LHAASO source has been found from the radio to sub-TeV bands. The LHAASO observations are consistent with the scenario that VHE electrons escaped from the pulsar, diffused in the interstellar medium, and scattered the interstellar radiation field. If interpreted as the pulsar halo scenario, the diffusion coefficient, inferred for electrons with median energies of ∼160 TeV, is consistent with those obtained from the extended halos around Geminga and Monogem and much smaller than that derived from cosmic ray secondaries. The LHAASO discovery of this source thus likely enriches the class of so-called pulsar halos and confirms that high-energy particles generally diffuse very slowly in the disturbed medium around pulsars.

[Efficacy analysis of fully endoscopic microvascular decompression in primary trigeminal neuralgia via keyhole approach].

Objective: To explore the efficacy and technical features of fully endoscopic microvascular decompression(MVD) in primary trigeminal neuralgia(PTN) via keyhole approach. Methods: The clinical data of 97 patients with PTN underwent fully endoscopic MVD via keyhole approach in the Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University from December 2014 to February 2019 was collected. During fully endoscopic MVD in PTN via keyhole approach, performer use natural clearance without grinding except developed rock bone crest or excessive retraction of the brain tissue, visually and panoramically observe and evaluate the CPA area, accurately identify the responsible vessels, to avoid the omission of responsible vessels or insufficient decompression. And the use of preplaced technology, bridging technology and submersible technology, ensure the efficacy of surgery and reduce the surgical side injuries.Barrow Neurological Institute (BNI) pain score was used to evaluate the efficacy and identify the recurrence. The surgical efficacy was analyzed. Results: The offending vessels were identified under endoscope in 96 cases. Among them, arterial compression was found in 77 cases, venous compression in 6 cases, and both arterial and venous compression in 13 cases. About the pain outcomes, 87 cases had immediate and complete relief of pain, 5 cases had almost relief of pain, 4 cases had partial relief of pain, and still needed medication control, but the dose was lower than that before operation, and 1 case had no obvious relief of pain. About complications, there were 4 cases of temporary facial numbness, 1 case of temporary hearing loss, both of them recovered after symptomatic treatment. There was no cerebral infarction or hemorrhage, intracranial or incision infection. All cases were followed up for 3.0-38.0 months with a median period of(22.4±2.2) months. During the follow-up periods, postoperative recurrence occurred in 3 cases. Conclusion: Fully endoscopic MVD for PTN through keyhole approach, provides panoramic view to avoid omission of offending vessels and reduce complications, seemed to be a safe and effective surgical method.

[Clinicopathological features and prognosis of nodal nevi].

Objective: To investigate the clinicopathological characteristics, differential diagnosis and prognosis of nodal nevi (NN). Methods: Eighteen cases of NN diagnosed at Fudan University Shanghai Cancer Center, Shanghai, China from 2009 to 2019 were collected. The clinicopathological characteristics and follow-up data were retrospectively analyzed. Histopathologic evaluation and immunohistochemical studies were carried out. The Vysis Melanoma FISH Probe Kit, combined with 9p21(CDKN2A) and 8q24(MYC) assays were performed in 2 cases. Results: There were 2 males and 16 females in the case series. The age of the patients ranged from 36 to 70 years (average 48.2 years). Fifteen cases located in axillary lymph nodes, 1 in inguinal lymph node, 1 in cervical lymph node, and 1 in external iliac lymph node. NN was found in only one lymph node in each case. Histologically, the nevus cell aggregates were found in capsule of lymph nodes in all cases. Nevus cells grew along the capsule into trabeculae in 8 cases, with 3 of them scattered in parenchyma. In one of these 8 cases, nevus cell aggregates massively occupied the parenchyma of the lymph node. The largest lesions in the 18 NN cases measured from 0.2 to 6.5 mm. All of the NN cases were classified as conventional nevi. The majority of the cases were composed of uniform nevus-like cells and identical to cutaneous pigmented nevi without atypia, necrosis, or mitosis. In the NN case that massively occupied parenchyma, some areas had abundant nevus cells and displayed atypical cytologic features, including increased nucleo-cytoplasmic ratio, small nucleoli, and occasional mitotic figures. Immunohistochemistry was performed in 13 cases. All of them were positive for S-100, SOX10, Melan A, and p16. HMB45 showed weak staining in rare cells of only one case out of 13 cases. Ki-67 labeling index <1% was found in all 13 cases. Additionally, the results of FISH assay were both negative. All patients were followed up for 13 to 129 months (median 31.5 months). Except that one patient died of the salivary gland carcinoma, the other patients all survived without tumor during the follow-up period. Conclusions: NN is a benign melanocytic lesion in lymph node. It is important to distinguish NN from metastatic melanoma when nevus cells occur in parenchyma and subcapsular sinus of lymph nodes, or show some atypical cytologic features. The morphology of bland nevus cells in capsule and trabeculae is a valuable clue. Besides, immunohistochemical profiling and FISH assay are helpful in the differential diagnosis.

SOCS2 affects the proliferation, migration and invasion of nasopharyngeal carcinoma cells via regulating EphA1.

Although the incidence of nasopharyngeal carcinoma (NPC) is relatively low, the mortality is very high and the patients have a poor prognosis. Thus, it is urgent to find a novel biomarker and a new therapeutic strategy. Suppressor of cytokine signaling-2 (SOCS2) was reported to be associated with various malignancies. However, the exact role of SOCS2 in NPC still remains largely unsure. In the present study, we showed that the expression of SOCS2 was significantly upregulated in NPC patients and cells. And the high expression of SOCS2 predicted a worse outcome in NPC patients. Moreover, the in vivo experiments indicated that knockout of SOCS2 inhibits the proliferation, migration, and invasion of NPC cells. Besides, we found a positive relationship between SOCS2 and EphA1 in NPC tissues. The rescue experiments indicated that SOCS2 affected the malignancy of NPC cells by regulating the expression of EphA1. Altogether, our data uncovered the ontogenetic role of SOCS2 dysregulation during the tumorigenesis of NPC. SOCS2 might serve as a biomarker during the diagnosis and treatment of NPC. And targeting SOCS2 might provide a novel treatment strategy for NPC patients.

Progress in Research on Biomarkers of Post-Traumatic Epilepsy.

ABSTRACT: Post traumatic epilepsy （PTE） is a serious complication of traumatic brain injury and a difficult problem in forensic justice practice. In recent years, many biomarkers have been applied to the diagnosis, treatment and prognosis of injuries and diseases. There have been many studies on the biomarkers of PTE in the field of epilepsy. This paper reviews the progress in research on biomarkers of PTE in recent years in order to provide reference for the forensic identification of PTE.

Bacillus licheniformis, a potential probiotic, inhibits obesity by modulating colonic microflora in C57BL/6J mice model.

AIMS: This study evaluated the effects of a potential probiotic, Bacillus sp., on the growth, serum and hepatic triglyceride, histological features of liver tissues and colonic microflora in high-fat diet-induced obese mice. METHODS AND RESULTS: Sixty male C57BL/6J mice were randomly divided into five groups: mice fed a low-fat diet (Cont), mice fed a high-fat diet (Hf), Hf and orally challenged with Bacillus subtilis (Bs), B. licheniformis (Bl) and a mixture of B. subtilis and B. licheniformis (Bls). Gavage feeding was provided at week 9 and the experiment was continued for 8 weeks. Treatment with B. licheniformis and a mixture of Bacillus sp. attenuated body weight gain at the end of study and enhanced glucose tolerance by sensitizing insulin action in the Hf-fed mice. Lower serum and hepatic triglyceride and epididymal fat weight were observed in Bl and Bls groups than that of Hf group. Lesser hepatic fat deposition was observed in the Bl and Bls groups than in the Hf group. High-throughput sequencing showed that Bacillus sp. supplementation dramatically changed the colonic bacterial community in obese mice. CONCLUSIONS: Bacillus licheniformis reduced body weight and improved glucose tolerance, obesity and insulin resistance in Hf-fed mice by changing colonic microbiota composition. SIGNIFICANCE AND IMPACT OF THE STUDY: Orally administration of Bacillus licheniformis may reduce body weight and decrease fat deposition by modulating colonic bacterial community in Hf model.

[The prostate cancer precision screening program: a preliminary report after recruitment of 2 159 men].

Objective: The Chinese Anti-Cancer Association Genitourinary Cancer Committee Prostate Cancer Working Group released Consensus of prostate cancer (PCa) screening in 2017. This program aims to evaluate the methods and significance of prostate cancer precision screening in high risk population. Methods: A total of 2 159 eligible males enrolled from 13 community centers and 3 screening centers received PSA test from April 2017 to August 2018. Prostate-specific antigen (PSA) determination in serum with a cut-off of ≥4.0 ng/ml was the main screening test and indication for biopsy. The interviewer-administered questionnaire covered demographic characteristics and environmental exposure factors. The associations between these factors and prostate cancer risk were determined by multivariable unconditional logistic regression models. Results: Altogether, 271 cases (12.6%) had a confirmed PSA increase ≥ 4.0 µg/L (median 9.1, range 4.0-25.0). Subsequently, 57 subjects (21.0%) out of the 271 PSA-suspicious men underwent prostate biopsy, and 34 (59.6%) were confirmed as prostate cancer. Until now, the overall prostate cancer incidence in the first screening round was1.57%. There were no statistical differences in the distributions of PSA-suspicious and prostate cancer incidence between community centers and screening centers (P=0.578 and 0.735). Age (OR: 2.63; 95%CI: 1.84-3.75, P<0.001) and chronic prostatitis history (OR: 2.02; 95%CI: 1.55-2.63, P<0.001) were significantly associated with PSA level. After adjustment for these factors, older age (OR: 4.04; 95%CI: 1.71-9.59, P=0.002) and statins use (OR: 3.09; 95%CI: 1.25-7.69, P=0.015) were associated with an elevated risk of PCa. Conclusions: It is of substantial significance to screen prostate cancer in high risk population. Both community centers and screening centers methods are effective. Although largely underestimated, the incidence of PCa in the targeted Chinese population is higher than expected. Older men have a high risk of harboring PCa. Our study suggests a decreased risk of PCa in men with statins use. Prostate Cancer Precision Screening is promising to improve prostate cancer survival in China.

[Application of complete endoscopic technique in microvascular decompression related tovertebrobasilar artery compression].

Objective: To study the operative method, special technique and curative effect of complete neuroendoscopic microvascular decompression(MVD) related to vertebrobasilar artery compression. Methods: Thirteen patients with functional cranial nerve disease caused by vertebrobasilar artery as direct or indirect responsible vessel accepted complete endoscopic MVD, including 11 patients with hemifacial spasm and 2 patients with trigeminal neuralgia. The procedure and curative effect of endoscopic surgery were analyzed retrospectively. Results: All procedures of complete neuroendoscopic MVD were successfully completed.Intraoperative observation by endoscope showed that 6 cases were oppressed directly by vertebral artery, 2 cases were oppressed directly by basilar artery, 5 cases were combined oppressed by displaced basilar artery and other vessels (1 case was superior cerebellar artery and 4 cases were anterior inferior cerebellar artery). During the operation, Teflon sheets was placed directly into the compression point in 2 cases, the "Pre-placed" technique was used to place Teflon sheets in 7 cases, and the "Set up bridge" technique was used to place Teflon sheets in 4 cases. Follow-up for 8-38 months,the symptoms disappeared completely in 12 cases and improved in 1 case. No deaths and severe complications occurred, such as postoperative bleeding, cerebellar infarction and intracranial infection. Conclusion: MVD related to vertebrobasilar artery compression can be performed by complete neuroendoscopic technique, which can achieve sufficient decompression effect and curative effect.Flexible use of the special technology of placing Teflon sheets by single-hand under endoscope, such as the "Pre-placed" and "Set up bridge" technique, is an important technical guarantee for the successful completion of endoscopic MVD.

[Efficacy analysis of soft neuroendoscopic techniques in the treatment of chronic subdural hematoma].

Objective: To investigate the efficacy of soft neuroendoscopic techniques in the treatment of chronic subdural hematoma (CSDH). Methods: A retrospective analysis of 201 cases of CSDH diagnosed and treated at Beijing Shijitan Hospital (CMU) from January 2006 to December 2017 was conducted. From January 2006 to December 2010, 126 cases of CSDH were treated with skull drilling and drainage (non-endoscopic group). From January 2011 to December 2017, 75 cases of CSDH were treated with soft neuroendoscopy (endoscopic group). The operation time of the non-endoscopic and endoscopic groups, the hematoma clearance rate on the first day after surgery, the time of the drainage tube, the length of hospital stay, the incidence of complications, mortality and recurrence rate were compared. Results: There were no deaths in both groups. The average operation time of the non-endoscopic group was 43 min, compared with the average operation time of the endoscopy group of 50 min, there was no significant difference (P>0.05). The average hematoma clearance rate on the first day after surgery in the endoscopy group (98.2%) was significantly higher than that in non-endoscopic group (87.3%) (P<0.01). The average time of drainage tube in the endoscopy group (23 h) was significantly shorter than that in the non-endoscopic group (50 h) (P<0.01). On the first postoperative day, the proportion of patients with mRS≤3 in the endoscopic group was significantly higher than that in the non-endoscopic group (P<0.01). At the time of discharge, the proportion of patients with mRS≤3 in the endoscopy group was also significantly higher than that in the non-endoscopic group, P<0.05. There was no significant difference in the average hospital stay between endoscopy group (7 d) and non-endoscopic group (8 d) (P>0.05). The postoperative complication rate in the endoscopy group was significantly lower than that in the non-endoscopic group (P<0.01). During 0.5-8 years of follow-up, the recurrence rate of CSDH in the endoscopic group (5.33%) was significantly lower than that in the non-endoscopic group (15.07%) (P<0.01). Conclusion: The application of visualization features of soft neuroendoscopy in the treatment of CSDH can significantly improve hematoma clearance, shorten the time of drainage tube, reduce postoperative complications and recurrence rate, and improve surgical outcomes.

[Chemotherapy combined with androgen-deprivation therapy in high-volume metastatic hormone sensitive prostate cancer: a short-term efficacy and safety analysis].

Objective: To investigate the short-term efficacy and adverse events of chemotherapy combined with androgen-deprivation therapy in high-volume metastatic hormone sensitive prostate cancer. Methods: From March 2015 to August 2017, 55 patients with high-volume metastatic hormone sensitive prostate cancer were enrolled at Department of Urology, Fudan University Shanghai Cancer Center receiving chemotherapy combined with androgen-deprivation therapy. The age was 65(8) years (M(Q(R))) (range: 46 to 79 years). Patients were enrolled in the study for continuous androgen-deprivation therapy (medical or surgical castration), combined with docetaxel 75 mg/m(2) intravenous injection on the first day, repeated every 21 days (6 cycles). Endpoints included overall survival, progression-free survival of prostate cancer, prostate specific antigen (PSA) response rate, and adverse events. Results: The follow-up time was 21.2(11.7) months. The PSA value before chemotherapy was 144.9(415.3) µg/L. The days in patients undergoing androgen deprivation therapy before chemotherapy was 14(23) days. Four patients (7.3%) presented 0 in Eastern Cooperative Oncology Group scoring system and 51 patients(92.7%) presented 1. Thirty-nine patients (70.9%) completed more than 6 cycles of combined chemotherapy, 17 patients (30.9%) showed PSA<0.2 µg/L at 6 months after treatment, and 14 patients (25.5%) showed PSA<0.2 µg/L at 12 months after treatment. Twenty-eight patients (50.9%) had grade 3 to 4 neutropenia and 1 patient (1.8%) developed infectious neutropenia and died. Nausea and vomit occurred in 16 patients (29.1%). Twelve patients (21.8%) underwent dose adjustment due to adverse events in blood system. Conclusions: The short-term effect was confirmed in high-volume metastatic hormone sensitive prostate cancer using chemotherapy combined androgen-deprivation therapy, and the long-term effect remains to be seen. Myelosuppression during chemotherapy requires close attention, and taking timely examination is recommended.

Rheumatoid arthritis fibroblast-like synoviocytes co-cultured with PBMC increased peripheral CD4+ CXCR5+ ICOS+ T cell numbers.

'Circulating' T follicular helper cells (Tfh), characterized by their surface phenotypes CD4+ chemokine receptor 5 (CXCR5)+ inducible co-stimulatory molecule (ICOS)+ , have been identified as the CD4+ T cell subset specialized in supporting the activation, expansion and differentiation of B cells. Fibroblast-like synoviocytes (FLS) are critical in promoting inflammation and cartilage destruction in rheumatoid arthritis (RA), and the interaction between FLS and T cells is considered to facilitate FLS activation and T cell recruitment. However, it remains unknown whether RA-FLS co-cultured with activated peripheral blood mononuclear cells (PBMC) has immunoregulatory effects on peripheral Tfh. In the present study, we co-cultured RA-FLS with or without anti-CD3/CD28-stimulated PBMC. The results showed that RA-FLS co-cultured with stimulated PBMC could increase the numbers of CD4+ CXCR5+ ICOS+ T cells of RA PBMC possibly via the production of interleukin (IL)-6, a critical cytokine involved in the differentiation of Tfh cells. We also observed increased reactive oxygen species (ROS) levels in the co-culture system of RA-FLS and PBMC. The percentage of CD4+ CXCR5+ ICOS+ T cells was decreased when ROS production was inhibited by N-acetyl-L-cysteine (NAC), a specific inhibitor which can decrease ROS production. In addition, we showed that the higher levels of tumour necrosis factor (TNF)-α and IL-1ß in the co-culture system and the blocking of TNF receptor 2 (TNF-R2) and IL-1ß receptor (IL-1ßR) both decreased the numbers of CD4+ CXCR5+ ICOS+ T cells. Our study reveals a novel mechanistic insight into how the interaction of RA-FLS and PBMC participates in the RA pathogenesis, and also provides support for the biologicals application for RA.

[Effect of home noninvasive positive pressure ventilation on patients with severe stable chronic obstructive pulmonary disease: a meta-analysis].

Objective: To evaluate the effect of home noninvasive positive pressure ventilation (NPPV) on patients with severe stable chronic obstructive pulmonary disease(COPD) by meta-analysis. Methods: The data of this meta-analysis was retrieved from the PubMed, EMBASE, Cochrane library, Wanfang, Weipu and CNKI databases from January 1980 to January 2016. Randomized controlled trials (RCTs) on comparison of the effect of home NPPV in patients with severe stable COPD were enrolled. The enrolled data were divided into different subgroups in terms of the levels of inspiratory positive airway pressure(IPAP), different duration of ventilation per day, and different levels of baseline hypercapnia on change in PaCO(2). Meta-analysis was performed to compare the effect of different subgroups by RevMan 5.3. Results: Ten studies with a total of 789 patients were included. Home NPPV improved 6-minute walk distance (WMD: -45.12, 95%CI: -85.39--4.85, P=0.03) and forced expiratory volume in the first second [standard mean difference(SMD): -0.26, 95%CI: -0.51--0.02, P=0.03]after 1 year of ventilation, but did not improve the mortality, PaCO(2,)PaO(2,)pH, FVC, maximal inspiratory pressure (MIP), FEV(1)/FVC, maximal voluntary ventilation(MVV) total sleep time, sleep efficiency and the proportion of rapid eye movement (REM) sleep. Subgroup analysis showed that home NPPV can significantly reduce the PaCO(2) in patients ventilated with 18 cmH(2)O(1 cmH(2)O=0.098 kPa) and higher IPAP levels than those with lower IPAP levels (SMD: -0.6, 95%CI: -1.09--0.12, P=0.01), and in patients with NPPV for at least 5 h per day and those with lower duration (SMD: -0.45, 95%CI: -0.87--0.02, P=0.04), and in patients with baseline PaCO(2) of at least 55 mmHg (1 mmHg=0.133 kPa) (SMD: -0.69, 95%CI: -1.07--0.31, P=0.00) than those with lower levels. Conclusions: Home NPPV can improve 6MWD and FEV(1) in severe stable COPD patients but does not improve the mortality, gas exchange and sleep efficiency. Patients may gain more benefits when using higher IPAP levels, longer ventilation per day and in those with higher baseline PaCO(2).

[Use of prostate health index in diagnosing prostate cancer in Chinese men].

Objective: To investigate the value of prostate health index (PHI) in the diagnosis of prostate cancer in patients with total prostate specific antigen (tPSA) <20 µg/L. Methods: Totally 1 135 patients with tPSA<20 µg/L and prostate biopsy indications at Department of Urology, Fudan University Shanghai Cancer Center from March 2013 to April 2016 were enrolled in this study. They were tested for serum tPSA, free prostate specific antigen and prostate specific antigen isoform 2, from which PHI was calculated. Diagnostic efficacy of PHI and tPSA were evaluated using receiver operating characteristic (ROC) curve analysis. The detection rates of prostate cancer were calculated in different ranges of PHI. Subgroup analysis of 716 patients, who were aged 50 or above with tPSA in the range of 4 to 10 µg/L and digital rectal examination negative, was performed. Results: In the biopsied objects with tPSA<20 µg/L, PHI was significantly higher in prostate cancer patients than that in non-cancer patients (48.4(37.4) vs. 26.5(16.9), U=52 674.00, P=0.000), PHI was also significantly higher in high-grade prostate cancer patients than that of low-grade prostate cancer patients (44.5(30.8) vs. 56.4(42.5), U=23 314.00, P=0.000). The area under the curve (AUC) of PHI for diagnosing prostate cancer was significantly higher than that of tPSA (0.771 vs. 0.627, P=0.000). When PHI was in the range of <27, 27 to <36, 36 to <55 and ≥55, the probability of prostate cancer was 9.4% (95%CI: 7.0% to 12.2%), 16.3% (95%CI: 12.2% to 20.8%), 31.0% (95%CI: 25.9% to 37.3%) and 66.4% (95%CI: 58.9% to 74.2%), respectively. Subgroup analysis showed that the AUC of PHI in diagnosing prostate cancer was significantly higher than that of tPSA (0.764 vs. 0.569, P=0.000). When PHI was in the range of <27, 27 to <36, 36 to <55 and ≥55, the probability of prostate cancer was 8.1% (95%CI: 5.4% to 11.3%), 14.0% (95%CI: 9.1% to 19.9%), 30.8% (95%CI: 23.6% to 38.7%) and 78.8% (95%CI: 66.7% to 88.9%), respectively. Conclusion: PHI is superior to tPSA in the diagnosis of prostate cancer in Chinese men with tPSA<20 µg/L.