Salvage endoscopic surgery for skull base osteoradionecrosis in nasopharyngeal carcinoma patients: A prospective, observational, single-arm clinical study.

BACKGROUND: Postradiation skull base osteoradionecrosis (ORN) is a severe complication that occurs after radiotherapy in patients with nasopharyngeal carcinoma (NPC) that can severely affect quality of life (QOL) and be life threatening. Only 13.4% - 28.6% of patients can be cured by traditional repeated endoscopic debridement. Here, we introduced salvage endoscopic surgery for skull base ORN patients and evaluated its clinical efficacy. METHODS: This was a prospective, observational, single-arm clinical study. Clinical data from 18 skull base ORN patients who underwent radical endoscopic necrectomy followed by reconstruction using a septal pedicled mucosal flap or temporal muscle flap were included in the study. The endpoint was an overall survival (OS) of 2 years. The numeric rating scale (NRS) scores for pain and foul odor were analyzed to determine the efficacy and safety of this surgery. RESULTS: A total of 21 patients were recruited, 18 of whom completed the study and were analyzed. All surgeries were successfully performed. During the 2-year study, the OS rate of the entire cohort was 75%. The median NRS score for pain decreased from 6.44 +- 2.62 to 0.50 +- 0.71, and the NRS score for foul odor decreased from 1.89±1.08 to 1 after surgery. CONCLUSIONS: Salvage endoscopic necrectomy followed by construction using a septal pedicled mucosal flap or temporal muscle flap is a novel, safe, and effective treatment for ORN in patients with NPC. CLINICAL TRIAL REGISTRATION: This study was approved by the independent ethics committee of the Eye, Ear, Nose and Throat Hospital of Fudan University (IEC No. 2019095-1). Written informed consent was obtained from all patients. The study was registered with the Chinese Clinical Trial registry (ChiCTR2000029327).

Simulating nitrogen balance in Canadian agricultural soils from 1981 to 2016.

Agriculture produces food, fiber and biofuels for the world's growing population, however, agriculture can be a major contributor of nitrogen (N) losses including emissions of ammonia (NH3), nitrous oxide (N2O) and nitrate (NO3-) leaching and runoff. A Canadian Agricultural Nitrogen Budget for Reactive N (CANBNr) model was developed to estimate the soil N balance in 3487 soil landscape of Canada polygons from 1981 to 2016. The CANBNr model integrates NH3 emission from fertilizers, manure from housing, storage and field, as well as direct/indirect N2O emissions from fertilizers, manures, crop residues and soil organic matter. The NO3- leaching is estimated based on the residual soil N (RSN) at harvest and drainage derived with the DeNitrification-DeComposition (DNDC) model. From 1981 to 2016, the N input from fertilizer and N fixation increased at a greater rate than N removal in harvested crops in all provinces of Canada, resulting in an increase in the RSN and N losses. In 2016, the Prairie provinces had lower N losses (11.7 kg N ha-1) from N2O, NH3 and NO3- compared with 43.2 kg N ha-1 in central Canada, and 76.5 kg N ha-1 in Atlantic Canada. However, the Prairie provinces had 84.3% of the total Canadian farmland (74.3% of the total Canadian N input), while central Canada had 12.9% of Canadian farmland (21.7% of the total Canadian N input). In the Prairie provinces, the total N2O loss from fertilizer N ranged 4.4-8.6 Gg N whereas NH3 loss ranged from 17.1 to 44.6 Gg N and these values were influenced by both emission intensity and total land area. Total N2O losses from manure were highest in Alberta, Ontario and Quebec resulting in 4.8, 4.4, and 3.4 Gg N and NH3 losses from manure were also highest in these 3 provinces at 61.1, 45.2 and 40.4 Gg N, respectively. Nitrate leaching was impacted by drainage volumes, soil type and N inputs. In the non-growing season, NO3- leaching losses (36-yr average) were 63.3 Gg in Ontario and 57.5 Gg N in Quebec compared with 20.8 Gg N for Ontario and 35.5 Gg N for Quebec in the growing season. In contrast, the Prairie provinces showed higher NO3- leaching in the growing season (23.1-37.4 Gg N) than in the non-growing season (10.4-13.7 Gg N). In summary, total fertilizer N increased the most over the 36 years in the Prairies which resulted in increased RSN and N leaching losses that will require further intervention.

[Phenotypic and genotypic characteristics of Escherichia coli causing bloodstream and abdominal co-infection].

Objective: To analyze the phenotypic and genotypic characteristics of Escherichia coli causing bloodstream and abdominal co-infection (CoECO), and provide clues for empirical antibiotics treatment. Methods: The strains of Escherichia coli isolated from blood and abdominal samples in the Department of Laboratory Medicine of the First Medical Center of the PLA General Hospital from 2010 to 2020 were retrospectively analyzed. Mass spectrometer was used to identify all of the strains and the minimum inhibitory concentration (MIC) were detected by VITEK 2 Compact. All isolates were sequenced by 2×150 bp double terminal sequencing strategy on the HiSeq X Ten sequencer (Illumina). After the genome sequence was spliced, the single nucleotide polymorphism (SNP) analysis of the strain sequence was performed using kSNP3 software to clarify the homologous relationship between strains. If the strains isolated from two different parts had high homology, they were regarded as the same strain and the case was with CoECO infection. Meanwhile, the multilocus sequence type (MLST) was determined using PubMLST website and resistant genes were screened by CARD website. Results: A total of 70 cases of CoECO infection were screened, including 45 males and 25 females, and aged (59.2±16.3) years old. The 70 CoECO isolates belonged to 35 sequence types (STs). The most prevalent STs included ST38 (n=6), ST 405 (n=6), ST 1193 (n=6) and ST131 (n=5), and other ST types contained less than 5 strains. The homologous relationship among strains was relatively scattered, presenting a sporadic trend as a whole, and only a few strains had a small-scale outbreak. The CoECO isolates showed significantly resistance to ampicillin (91.4%, 64/70), ampicillin/sulbactam (74.3%, 5 2/70), ceftriaxone (72.9%, 51/70), ciprofloxacin (71.4%, 50/70) and levofloxacin (71.4%, 50/70), and high-sensitivity to piperacillin/tazobactam, carbapenems and amikacin. The most prevalent resistant gene was tet (A/B) (70%, 49/70), followed by blaTEM (58.6%, 41/70), sul1 (55.7%, 40/70), sul2 (54.3%, 38/70), blaCTX-M-14(25.7%, 18/70), blaCTX-M-15(17.1%, 13/70), blaCTX-M-55(15.7%, 11/70), blaCTX-M-64/65(5.7%, 4/70), blaCTX-M-27(4.3%, 3/70), mcr-1 (4.3%, 3/70), blaNDM-5(2.9%, 2/70). Conclusions: CoECO is distributed dispersedly and has no obvious advantage clone. No genotype with obvious advantages was found. Although the strain has a high resistance rate to some antibacterial drugs, the proportion of carrying resistant genes is low, and it has a high sensitivity to some first-line antibacterial drugs.

[Attention should be paid to the lifelong monitoring of diabetic retinopathy in people with diabetes].

Diabetic retinopathy (DR) is one of the severe complications of diabetes, and also the most common reason of vision loss in Chinese adults over 30 years old. Regular fundus examination and continuous glucose monitoring can prevent 98% of blindness caused by DR. However, due to the irrational allocation of medical resources and the weak awareness of DR patients, only about 50% to 60% of diabetes patients have an annual DR screening. Therefore, it is necessary to build a follow-up system for early screening, prevention, treatment and lifelong monitoring of DR patients. In this review, we discuss the importance of lifelong monitoring, the hierarchical medical system and the follow-up of pediatric DR patients. Novel and multi-level screening methods are cost-saving to patients and cost-effective to healthcare systems, and also can help improve the detection and early treatment of DR.

[Research progress on infiltrating zone and microvascular invasion of hepatic alveolar echinococcosis].

Hepatic alveolar echinococcosis (AE) is a parasitic disease with biological characteristics similar to malignant tumor. It has no obvious clinical symptoms in the early stage. Most patients have complications such as jaundice, ascites and gastrointestinal bleeding when they see a doctor. At this time, the course of disease is at an advanced stage. In addition, the incomplete resection of the AE lesion(s) leads to a high postoperative recurrence rate, which has a serious impact on the physical and mental health of patients. Based on the summary of the latest research at home and abroad and the analysis of blood supply, microvascular invasion and vascular growth factor expression in the "infiltrating zone" adjacent to the lesions of hepatic AE, this article has a deep understanding of the occurrence and development process of hepatic AE, aiming to better guide clinical practice and improve the quality of life of patients.

[Veracity of using a visual chart with a testing distance of 2.5 meters for measurement of distance visual acuity in teenagers].

Objective: To compare the results of visual acuity testing for teenagers with visual acuity charts designed at 2.5-meter and 5-meter distances, and to investigate the accuracy of the 2.5-meter visual acuity chart. Methods: It was a self-control study. A total of 227 teenagers (454 eyes) with ametropia who came to the ophthalmic clinic of Peking Union Medical College Hospital from March 2019 to September 2019 were included. There were 123 males and 104 females aged (11.74±3.26) years. The vision examiners were trained in the same testing environment and passed the consistency test. Distance visual acuity of all participants was tested with charts designed at 2.5 meters and 5 meters in a 10-minute interval. According to the age (7-9, 10-12, 13-15 and 16-18 years old) and visual acuity (1.00-0.52, 0.40-0.30 and 0.22-0.10), the results of two kinds of visual acuity charts were compared. The testing order of the two visual charts was randomly determined. The visual acuity results were converted into logMAR values and compared. Paried t-student test was used to compare the difference between two charts, and Pearson correlation test was used to explore the correlation between the results of two charts. Results: The visual acuity of the right eye was 0.37±0.24 (logMAR) at 2.5 meters and 0.50±0.26 (logMAR) at 5 meters. The distance visual acuity measured with the 2.5-meter visual acuity chart was better (t=16.19, P<0.01). The visual acuity of the left eye was 0.36±0.23 (logMAR) at 2.5 meters and 0.45±0.23 (logMAR) at 5 meters (t=11.71, P<0.01). The differences between two charts were larger among teenagers with lower visual acuity (r=0.387,P<0.01). Conclusion: Under the same test conditions, the distance visual acuity measured with a 2.5-meter chart was significantly better than a 5-meter chart. The visual acuity chart designed at 2.5 meters was not an appropriate tool to measure distance vision in adolescents. (Chin J Ophthalmol, 2021, 57: 122-125).

A retrospective cohort study of early mortality among patients with HIV/TB co-infection in Shanghai municipality.

OBJECTIVES: Tuberculosis (TB) is the most common and fatal opportunistic co-infection among HIV-infected individuals. While TB-associated mortality predominantly occurs in the first 90 days after admission, such a correlation remains unclear in HIV/TB co-infected patients. Thus, we aimed to investigate the 90-day mortality and associated risk factors among HIV/TB co-infected patients in China. METHODS: Adult patients with HIV and a newly confirmed TB diagnosis admitted to the Shanghai Public Health Clinical Center between September 2009 and August 2017 were enrolled. Clinical and laboratory characteristics, key treatments and outcomes were collected retrospectively. The associations between different factors and early mortality were analysed. RESULTS: Of the 485 laboratory-confirmed HIV/TB patients [median (range) age = 39 (19-79) years], 413 (85.15%) were male. Diagnosis was confirmed by culture, pathology and acid-fast bacilli smear alone in 362 (74.6%), 6 (1.2%) and 117 (24.1%) patients, respectively. Multiple drug-/rifampin-resistant TB was detected in 21 (5.8%) of the 367 patients with a positive culture. Rifampin or rifabutin was administered to 402 (82.9%) patients. Additionally, 66 (13.6%) and 86 (17.7%) died within 90 days and 1 year of admission, respectively. Of the 64 TB-related deaths, 59 (92.2%) occurred within 90 days of admission. In Cox regression, central nervous system (CNS) TB [odds ratio (OR) = 2.49, 95% confidence interval (CI): 1.46-4.23, P < 0.001], no antiretroviral therapy (ART) within 3 months after admission (OR = 11, 95% CI: 6.4-18.9, P < 0.001), and plasma albumin level < 25 g/L (OR = 1.91, 95% CI: 1.07-3.40, P = 0.021) were associated with early death. CONCLUSIONS: Tuberculosis co-infection was prevalent and fatal in HIV-infected patients, with most deaths occurring within 90 days of admission. Early mortality was associated with CNS-TB, no ART, and serum albumin level < 25 g/L.

[Clinical efficacy of surgical opportunity of the modified transvaginal cervicoisthmic cerclage in treatment of the cervical incompetence].

Objective: To explore the surgical opportunity of the transvaginal cervicoisthmic cerclage in the treatment of the cervical incompetence and the effect on the pregnancy outcomes. Methods: A Retrospective controlled trial was carried out between January 2014 and December 2018 in the Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital in Zhejiang, China and a total of 1 027 patients with cervical incompetence underwent the transvaginal cerclage. According to the different surgical opportunity, the patients were divided into two groups: the conception cerclage (n=736) and the preconception cerclage (n=291), and the former were divided into two subgroups depending on the condition of the cervix, the history indicated conception cerclage (n=511) and the ultrasound indicated conception cerclage (n=225). Main outcome measures were the gestational age, term delivery rate, the fetal weight and the fetal survival rate. Results: After the cerclage, the gestational age was (36±4) weeks, the term delivery rate was 69.6% (710/1 020), the fetal weight was (3 038±624)g and the fetal survival rate was 94.7% (966/1 020). Compared with the ultrasound indicated conception cerclage subgroup, the gestational age, the term delivery rate, and the fetal weight were all significantly higher in the history indicated conception cerclage subgroup [(37±4) vs (36±5) weeks, t=2.691; 72.8% vs 62.7%,χ(2)=7.593; (3 091±594) vs (2 963±756) g, t=2.396; all P<0.05], but the fetal survival rate was comparable in these two groups(95.3% vs 92.9%, χ(2)=1.772, P>0.05). There were no significant differences in the gestational age, the term delivery rate, the fetal weight and fetal survival rate between the history indicated conception cerclage and the preconception cerclage (all P>0.05). Conclusion: The transvaginal cervicoisthmic cerclage is a promising and safe technique for improving obstetric outcomes in women with cervical incompetence, and the history indicated conception cerclage is better than the ultrasound indicated cerclage.

[Establishment of mouse model and preliminary screening of serum biomarkers for Candidemia].

Objective: To establish mouse models of Candidemia, and investigates statistically significant polypeptide peaks to provide auxiliary diagnosis of this disease. Methods: A total of 170 specific pathogen free adult male ICR mice with body mass of 27-30 g were completely randomly divided into Candida albicans infection group (n=80), Candida parapsilosis infection group (n=80) and the normal control group (n=10), and the two kinds of Candidemia mouse models were established via tail vein injection. The serum samples were analyzed by Matrix-assisted laser desorption-ionization time of flight mass spectrometry and relevant software, and the polypeptide peaks with significant differences were screened to establish diagnostic models. Results: A total of 65 differential polypeptide peaks were obtained compared with the Candida albicans infection group and the normal control group. Combined with m/z 1 100.4, 1 581.0, 3 808.0 as differential polypeptide peaks to established the diagnostic model, the sensitivity was 95.24%(40/42), the specificity was 90.63%(29/32), the accuracy rate was 93.24%(69/74), and the AUC value of the ROC curve was 0.972(95%CI: 0.941-1.000). A total of 73 differential polypeptide peaks were obtained compared with Candida parapsilosis infection group and the normal control group. Combined with m/z 1 433.2, 1 148.5, 4 093.5, 4 522.2, 8 140.9, 8 234.6 as differential polypeptide peaks to established the diagnostic model, the sensitivity was 95%(38/40), the specificity was 81.25%(26/32), the accuracy rate was 88.89%(64/72), and the AUC value of the ROC curve was 0.953(95%CI: 0.903-1.000). A total of 78 differential polypeptide peaks were obtained compared with Candida albicans infection group and Candida parapsilosis infection group. Combined with m/z 2 736.9, 8 091.5, 8 153.7 as differential polypeptide peaks to established the diagnostic model, the accuracy of distinguishing C. albicans infection from C. parapsilosis infection was 98.78%(81/82). Conclusions: Successfully screened the differential polypeptides and established the related diagnostic models. Which is helpful to find serum biomarkers for the auxiliary diagnosis of Candidemia, and provides a basis for the early diagnosis and the rational use of drugs.

[Research of artificial intelligence-based clinical decision support system for primary hepatocellular carcinoma].

Objective: To apply artificial intelligence technology in clinical real-world data of patients with primary hepatocellular carcinoma, explore the precise treatment of disease and build up artificial intelligence-based clinical decision support system. Methods: A total of 5 642 patients with primary hepatocellular carcinoma admitted to West China Hospital from July 2004 to June 2016 with complete follow-up records were included in the study. A merged model composed of multiple sub-classifiers was adopted to calculate therapy recommendation coefficient, and receiver operator characteristic curve was analyzed. Survival risk and recurrence risk were predicted by DeepSurv algorithm, and Kaplan-Meier survival curves were further compared among low, middle and high risk groups. Siamese-Net was applied to find similar patients. Results: The Top-1 and Top-2 accuracy of therapy recommendation coefficient reached 82.36% and 94.13% respectively. In internal verification of West China Hospital, the above-mentioned value reached 95.10% in accordance with multi-disciplinary team results. The C-index derived from survival risk model was 0.735 (95%CI:0.70-0.77), and the difference of Kaplan-Meier in pairwise comparison was of statistical significance under log-rank test (P<0.001). Meanwhile, the C-index derived from recurrence risk model was 0.705 (95%CI:0.68-0.73), and the difference of Kaplan-Meier in pairwise comparison was of statistical significance under log-rank test (P<0.001). Conclusions: The artificial intelligence-based clinical decision support system for primary hepatocellular carcinoma has can accurately make therapy recommendation and prognosis prediction for primary hepatocellular carcinoma.

[Preliminary study of the relationship between novel coronavirus pneumonia and liver function damage: a multicenter study].

Objective: To analyze the clinical characteristics of cases of novel coronavirus pneumonia and a preliminary study to explore the relationship between different clinical classification and liver damage. Methods: Consecutively confirmed novel coronavirus infection cases admitted to seven designated hospitals during January 23, 2020 to February 8, 2020 were included. Clinical classification (mild, moderate, severe, and critical) was carried out according to the diagnosis and treatment program of novel coronavirus pneumonia (Trial Fifth Edition) issued by the National Health Commission. The research data were analyzed using SPSS19.0 statistical software. Quantitative data were expressed as median (interquartile range), and qualitative data were expressed as frequency and rate. Results: 32 confirmed cases that met the inclusion criteria were included. 28 cases were of mild or moderate type (87.50%), and four cases (12.50%) of severe or critical type. Four cases (12.5%) were combined with one underlying disease (bronchial asthma, coronary heart disease, malignant tumor, chronic kidney disease), and one case (3.13%) was simultaneously combined with high blood pressure and malignant tumor. The results of laboratory examination showed that the alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBil) for entire cohort were 26.98 (16.88 ~ 46.09) U/L and 24.75 (18.71 ~ 31.79) U/L, 39.00 (36.20 ~ 44.20) g/L and 16.40 (11.34 ~ 21.15) µmol/L, respectively. ALT, AST, ALB and TBil of the mild or moderate subgroups were 22.75 (16.31 ~ 37.25) U/L, 23.63 (18.71 ~ 26.50) U/L, 39.70 (36.50 ~ 46.10) g/L, and 15.95 (11.34 ~ 20.83) µmol/L, respectively. ALT, AST, ALB and TBil of the severe or critical subgroups were 60.25 (40.88 ~ 68.90) U/L, 37.00 (20.88 ~ 64.45) U/L, 35.75 (28.68 ~ 42.00) g/L, and 20.50 (11.28 ~ 25.00) µmol/L, respectively. Conclusion: The results of this multicenter retrospective study suggests that novel coronavirus pneumonia combined with liver damage is more likely to be caused by adverse drug reactions and systemic inflammation in severe patients receiving medical treatment. Therefore, liver function monitoring and evaluation should be strengthened during the treatment of such patients.

Anomalous Thermoelectric Effects of ZrTe_{5} in and beyond the Quantum Limit.

Thermoelectric effects are more sensitive and promising probes to topological properties of emergent materials, but much less addressed compared to other physical properties. We study the thermoelectric effects of ZrTe_{5} in a magnetic field. The presence of the nontrivial electrons leads to the anomalous Nernst effect and quasilinear field dependence of thermopower below the quantum limit. In the strong-field quantum limit, both the thermopower and Nernst signal exhibit exotic peaks. At higher magnetic fields, the Nernst signal has a sign reversal at a critical field where the thermopower approaches zero. We propose that these anomalous behaviors can be attributed to the gap closing of the zeroth Landau bands in topological materials with the band inversion. Our understanding to the anomalous thermoelectric properties in ZrTe_{5} opens a new avenue for exploring Dirac physics in topological materials.

Fuel-Composition Dependent Reactor Antineutrino Yield at RENO.

We report a fuel-dependent reactor electron antineutrino (ν[over ¯]_{e}) yield using six 2.8 GW_{th} reactors in the Hanbit nuclear power plant complex, Yonggwang, Korea. The analysis uses 850 666 ν[over ¯]_{e} candidate events with a background fraction of 2.0% acquired through inverse beta decay (IBD) interactions in the near detector for 1807.9 live days from August 2011 to February 2018. Based on multiple fuel cycles, we observe a fuel ^{235}U dependent variation of measured IBD yields with a slope of (1.51±0.23)×10^{-43} cm^{2}/fission and measure a total average IBD yield of (5.84±0.13)×10^{-43} cm^{2}/fission. The hypothesis of no fuel-dependent IBD yield is ruled out at 6.6σ. The observed IBD yield variation over ^{235}U isotope fraction does not show significant deviation from the Huber-Mueller (HM) prediction at 1.3 σ. The measured fuel-dependent variation determines IBD yields of (6.15±0.19)×10^{-43} and (4.18±0.26)×10^{-43} cm^{2}/fission for two dominant fuel isotopes ^{235}U and ^{239}Pu, respectively. The measured IBD yield per ^{235}U fission shows the largest deficit relative to the HM prediction. Reevaluation of the ^{235}U IBD yield per fission may mostly solve the reactor antineutrino anomaly (RAA) while ^{239}Pu is not completely ruled out as a possible contributor to the anomaly. We also report a 2.9 σ correlation between the fractional change of the 5 MeV excess and the reactor fuel isotope fraction of ^{235}U.

The overexpression of Fra1 disorders the inflammatory cytokine secretion by mTEC of myasthenia gravis thymus.

The thymus of a myasthenia gravis (MG) patient is often accompanied by and effected with follicular hyperplasia. Inflammatory cytokines in thymus induce the formation of germinal centres (GC). MG thymic inflammatory cytokines are predominantly secreted by stromal cells. Our previous studies revealed that the expression level of the Fra1 protein, which is a Fos member of the activator protein 1 transcription factors (AP-1), was higher in the MG thymus compared with that of the normal thymus. Based on that, we demonstrated that Fra1 was mainly expressed in medulla thymic epithelial cells (mTECs) and that the rate of Fra1 positive mTECs in the MG thymus was higher than normal. In vitro, we found that the expression of CCL-5, CCL-19 and CCL-21 could be regulated by Fra1 in mTEC and that IL-1ß, IL-6, IL-8 and ICAM1 were downregulated in the Fra1 overexpression group and upregulated in the Fra1 knock-down group. Meanwhile, we detected that the expression levels of suppressor of cytokine signalling 3 (SOCS3) were significantly upregulated along with the overexpression of Fra1. Hence, we considered that the overexpression of Fra1 disrupted inflammatory cytokine secretion by mTEC in the MG thymus and that STAT3 and SOCS3 were strongly involved in this process.

Measurement of Reactor Antineutrino Oscillation Amplitude and Frequency at RENO.

The RENO experiment reports more precisely measured values of θ_{13} and |Δm_{ee}^{2}| using ∼2200 live days of data. The amplitude and frequency of reactor electron antineutrino (ν[over ¯]_{e}) oscillation are measured by comparing the prompt signal spectra obtained from two identical near and far detectors. In the period between August 2011 and February 2018, the far (near) detector observed 103 212 (850 666) ν[over ¯]_{e} candidate events with a background fraction of 4.8% (2.0%). A clear energy and baseline dependent disappearance of reactor ν[over ¯]_{e} is observed in the deficit of the measured number of ν[over ¯]_{e}. Based on the measured far-to-near ratio of prompt spectra, we obtain sin^{2}2θ_{13}=0.0896±0.0048(stat)±0.0047(syst) and |Δm_{ee}^{2}|=[2.68±0.12(stat)±0.07(syst)]×10^{-3} eV^{2}.

A multicentre, open, investigator-initiated phase IV clinical trial to evaluate the efficacy and safety of ingenol mebutate gel, 0·015% on the face and scalp, and 0·05% on the trunk and extremities, in Korean patients with actinic keratosis (PERFECT).

BACKGROUND: Ingenol mebutate gel is a novel, field-directed topical treatment for actinic keratosis (AK). Most pivotal studies have targeted Western populations. No clinical study has been conducted to investigate its efficacy and safety in Asian populations. OBJECTIVES: To evaluate the efficacy and safety of ingenol mebutate gel for treating AK of face/scalp and trunk/extremities in a large Asian (Korean) population. PATIENTS AND METHODS: In this multicentre, open-label, interventional, parallel-group, prospective phase IV study (PERFECT, trial registration no.: NCT02716714), the eligible patients were allocated into either the face/scalp or the trunk/extremities group, according to their selected treatment area location. After application of ingenol mebutate gel, the participants were followed up for 6 months. The primary efficacy endpoint was complete clearance (CC) of AK lesions in the selected treatment area at day 57. Quality of life was evaluated using Skindex-29. Safety endpoints included local skin responses, scar, pigmentation, pain and adverse events. RESULTS: In total, 78·1% [95% confidence interval (CI) 66·86-86·92%] of subjects had CC at day 57, with 76·6% (95% CI 64·31-86·25%) in the face/scalp group and 88·9% (95% CI 51·75-99·72%) in the trunk/extremities group. Among them, CC was sustained in 88·9% (48 of 54, 95% CI 77·37-95·81%) at month 6. The local skin responses significantly increased 1 day after the treatment compared with baseline, and decreased afterwards. Among the total subjects, 7·8% (6 of 77) had hyperpigmentation on the application area. Scars were not reported. CONCLUSIONS: Ingenol mebutate is effective for the treatment of AK in Asians, with tolerable safety profiles.

[Efficacy of mesenchymal stem cells on systemic lupus erythematosus:a meta-analysis].

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease with multi-organ involvement and several typical autoantibodies. Mesenchymal stem cells (MSC) are multipotent stem cells with low immunogenicity that can differentiate into various kinds of cells, such as bone, cartilage, fat and skin tissue. MSC have immunomodulatory and reparative properties through interactions with immune cells. MSC have been used in the treatment of refractory SLE and lupus nephritis patients for more than ten years. Most clinical studies were self-controlled studies and only a few were randomized controlled trials. The objective of this study was to use meta-analysis method to evaluate the efficacy and safety of MSC treatment in SLE patients. METHODS: The PubMed, Cochrane Library, Wanfang and VIP databases were searched for published randomized controlled trials and self-controlled studies before June 1, 2018. The search terms included the Chinese and English versions of mesenchymal stem cells, Mesenchymal Stromal Cells [Mesh], systemic lupus erythematosus, lupus, Lupus Erythematosus, Systemic [Mesh]. Two authors independently screened the literatures, assessed the quality of the studies and collected data according to the inclusion and exclusion criteria. The endpoints were the SLE disease activity index, 24 h urine protein and complement C3. Meta-analysis was performed with the Revman 5.3 software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. RESULTS: Eight studies involving 213 patients were included and three of the studies were randomized controlled trials with 66 patients involved. The MSC group showed that the SLE disease activity index decreased significantly [standard mean difference (SMD)=-1.76, 95% confidence interval (CI): -2.00 to -1.51, P<0.001), the 24 h urine protein decreased significantly (SMD=-1.74, 95%CI: -2.46 to -1.03, P<0.001), as well as the complement C3 increased significantly (SMD=1.28, 95%CI: 0.93 to 1.62, P<0.001). Four studies reported adverse events including fever, diarrhea and headache during the infusion. CONCLUSION: Current evidences showed that MSC could improve the disease activity, proteinuria and hypocomplementemia in SLE patients. Large scale and high-quality randomized controlled trials are required to validate the efficacy and safety of MSC treatment in SLE patients.

[The significance of clinical indicators of different Gram-stained bacteria resulted in secondary intracranial infection after craniocerebral operation].

Objective: To compare and analyze the clinical characteristics and laboratory parameters of central nervous system (CNS) infection caused by different Gram-stained bacteria after craniocerebral surgery, and to provide a preliminary basis for early anti-infection treatment to reduce the use of extended-spectrum antibiotics and the generation of resistant strains. Methods: A single center retrospective study was conducted to investigate the clinical data of patients with intracranial infection after craniocerebral surgery from January 2012 to December 2016 in PLA general hospital. The general conditions, clinical features, laboratory parameters, antibiotic treatments and prognosis were analyzed. Results: A toal of 813 cases of CNS infection after craniocerebral surgery were found during the 5-year period, with an incidence rate of 5.43% (813/14 986). The positive rate of cerebrospinal fluid (CSF)culture was 9.72% (79/813). According to the criteria, 71 cases were included in the study. Among all the cases, 64.8% (46/71) of which were Gram-positive bacteria (G(+) ) and 35.2% (25/71) were identified as Gram-negative bacteria (G(-)). The duration between surgery and meningitis events, as well as the period of antibiotic treatment for G(+) bacteria group were 5.0 (4.0, 6.0) days and (18.3±6.8) days, which were shorter than those of the G(-) bacteria group 9.0(7.0, 11.0) days and (29.2±9.9) days (Z=-6.184, t=-5.245, both P<0.01) , and the differences were statistically significant. The serum procalcitonin concentration in the G(+) group was lower than that in G(-) group [1.02(0.83, 1.27)µg/L vs 2.68(1.97, 5.07)µg/L, Z=-5.719, P<0.01]. The cerebrospinal fluid glucose content was higher than that of G(-) bacteria group[(2.13±1.30) mmol/L vs (1.09±0.95) mmol/L, t=3.512, P<0.01]. The protein level was lower than that of G(-) bacteria group [(1 615.93±848.83) mg/L vs (2 480.60±1 105.28) mg/L, t=-3.679, P<0.01]. Serum C-reactive protein concentrations in the two groups did not show any statistical significance [(96.2±46.1) mg/L vs (117.8±46.3) mg/L, t=-1.884, P>0.05]. In addition, the mortality rate of the G(-) bacteria group was 16.0% (4/25), and 0 in G(+) bacteria group. Conclusion: The time of onset of intracranial infection, serum PCT concentration, and cerebrospinal fluid glucose and protein content caused by Gram-positive bacteria and Gram-negative bacteria are found to be significantly different, and these findings could serve as a preliminary guide for the selection of antibiotics in early experiential anti-infective treatments without the etiology report.

[The mechanism and current strategies for preventing the recurrence of hepatocellular carcinoma after liver transplantation].

The recurrence rate of hepatocellular carcinoma (HCC) after liver transplantation is still high, seriously affecting the long-term survival rate. The current research results show that the mechanism of postoperative recurrence of liver cancer is mainly related to residual micro-lesions, hepatitis, regeneration and immunosuppression. Milan criteria for liver transplantation, tumor vascular invasion, degree of differentiation, surgical procedures, and the use of calcineurin immunosuppressive agents are risk factors for recurrence of HCC after liver transplantation, and biomarkers such as genes and miRNAs that respond to biological characteristics of the tumor have been gradually used in HCC recurrence risk stratification and predicting prognosis. The use of mTOR inhibitors, preoperative interventional treatment before liver transplantation and non -tumor ablation technique are the main effective methods to prevent the recurrence of HCC. Hepatectomy is still the most effective treatment for patients with recurrent HCC after transplantation, and intervention with sorafenib in combination with mTOR inhibitors can benefit the survival of most patients.

Polyclonal Regulatory T Cell Therapy for Control of Inflammation in Kidney Transplants.

Early subclinical inflammation in kidney transplants is associated with later graft fibrosis and dysfunction. Regulatory T cells (Tregs) can reverse established inflammation in animal models. We conducted a pilot safety and feasibility trial of autologous Treg cell therapy in three kidney transplant recipients with subclinical inflammation noted on 6-month surveillance biopsies. Tregs were purified from peripheral blood and polyclonally expanded ex vivo using medium containing deuterated glucose to label the cells. All patients received a single infusion of ~320 × 106 (319, 321, and 363.8 × 106 ) expanded Tregs. Persistence of the infused Tregs was tracked. Graft inflammation was monitored with follow-up biopsies and urinary biomarkers. Nearly 1 × 109 (0.932, 0.956, 1.565 × 109 ) Tregs were successfully manufactured for each patient. There were no infusion reactions or serious therapy-related adverse events. The infused cells demonstrated patterns of persistence and stability similar to those observed in non-immunosuppressed subjects receiving the same dose of Tregs. Isolation and expansion of Tregs is feasible in kidney transplant patients on immunosuppression. Infusion of these cells was safe and well tolerated. Future trials will test the efficacy of polyclonal and donor alloantigen-reactive Tregs for the treatment of inflammation in kidney transplants.