[The value of minimal residual disease and IKZF1 deletion for predicting prognosis in adult patients with B-cell acute lymphoblastic leukemia].

Objective: To reassess the prognostic value of minimal residual disease (MRD) and IKZF1 gene deletions in adults with B-cell acute lymphoblastic leukemia (B-ALL) who received pediatric-specific chemotherapy regimens during the Nanfang Hospital PDT-ALL-2016 trial. Methods: We retrospectively analyzed the prognosis of 149 adult patients with B-ALL who were admitted to Nanfang Hospital from January 2016 to September 2020. Prognostic factors were identified using Cox regression models. Results: The complete remission rate was 93.2% in 149 patients, with a 5-year overall survival (OS) rate of (54.3±5.0) % and a cumulative incidence of relapse (CIR) of (47.5±5.2) %. The Cox regression analysis revealed that MRD positivity at day 45 (MRD(3)) after induction therapy was independently associated with relapse risk (HR=2.535, 95%CI 1.122-5.728, P=0.025). Deletion of IKZF1 gene was independently associated with mortality risk (HR=1.869, 95%CI 1.034-3.379, P=0.039). Based on MRD(3) and IKZF1 gene status, we categorized adult patients with B-ALL into the low-risk (MRD(3)-negative and IKZF1 gene deletion-negative) and high-risk (MRD(3)-positive and/or IKZF1 gene wild type) groups. The 5-year OS and CIR rates were (45.5±6.0) % vs (69.4±8.6) % (P<0.001) and (61.6±8.3) % vs (25.5±6.5) % (P<0.001), respectively, in the high-risk and low-risk groups, respectively. The multivariate analysis showed that the high-risk group was an independent risk factor for OS (HR=3.937, 95%CI 1.975-7.850, P<0.001) and CIR (HR=4.037, 95%CI 2.095-7.778, P<0.001) . Conclusion: The combined use of MRD and IKZF1 gene in prognostic stratification can improve clinical outcome prediction in adult patients with B-ALL, helping to guide their treatment.

[Single extract of Forsythia Suspense versus the prepared drug in pieces: comparison of their anti-inflammatory, antitumor and antibacterial effects in zebrafish].

OBJECTIVE: To compare the anti-inflammatory, antitumor and anti-bacterial effects of the single extract (in granules) and the prepared drug in pieces of Forsythia Suspense (Lianqiao, a traditional Chinese herbal medicine). METHODS: In zebrafish embryo models of CuSO4 exposure, tail transection and LPS microinjection-induced inflammation, the anti-inflammatory effects of 10 µg/mL DEX, single extract of Forsythia Suspense, and the water extract of the prepared drug (400, 600, and 800 µg/mL) were evaluated by observing neutrophil counts, RT- qPCR, HE staining and survival analysis. Zebrafish embryo models bearing different human tumor cell xenografts were used to assess the anti-tumor effect of the drugs in different dosage forms by fluorescence staining and HE staining. The microbroth dilution method was used to evaluate the antibacterial efficacy of the drugs. RESULTS: In the zebrafish embryo models of inflammation, both of the two dosage forms of Forsythia Suspense significantly inhibited neutrophil aggregation, reduced the mRNA expressions of TNF-α, IL-6, P38, Jnk, Erk and P65, and increased the survival rate of zebrafish. They both showed obvious inhibitory effects against xenografts of different human cancer cells including colon cancer cells (HCT116), pancreas adenocarcinoma cells (PANC-1), lung cancer cells (A549), liver cancer cells (Hep3B) and cervical carcinoma cells (Hela) in zebrafish embryos, and exhibited strong anti-bacterial effects at the concentration of 15.63 mg/mL. CONCLUSION: The two dosage forms of Forsythia Suspense have similar anti-inflammatory, antitumor and antibacterial effects, but their effects for inhibiting IL-6, P65, and Jnk mRNA expressions and HCT116 cell proliferation differ significantly at low doses in zebrafish.

[Epidemiological characteristics of typhoid fever in Fujian Province, 2011-2022].

Objective: To analyze the incidence trend and epidemiological characteristics of typhoid fever in Fujian Province from 2011 to 2022, and understand the high-incidence population and hotspot areas, and provide evidences to develop more targeted prevention and control measures. Methods: The surveillance data of typhoid fever during 2011-2022 in Fujian Province were obtained from the National Disease Reporting Information System and analyzed with SAS 9.4. The spatial autocorrelation analysis of typhoid fever incidence at county/district levels was performed with ArcGlS 10.8. Results: A total of 5 126 cases of typhoid fever were reported in Fujian Province from 2011 to 2022, with an average annual incidence rate of 1.10/100 000. The average annual incidence rate was 0.96/100 000 from 2011 to 2015, 1.49/100 000 from 2016 to 2019, and 0.81/100 000 from 2020 to 2022. The disease occurred all the year round, with high epidemic season from May to September. A total of 23.59% (1 209/5 126) of the cases occurred at the age of 0-4, and 9.62% (493/5 126) at the age of 5-9. The male to female ratio of the cases was 0.97∶1 (2 524∶2 602) for the whole population, 1.19∶1 (925∶777) for people under 10 years old, 0.75∶1 (1 060∶1 404) for people between 10 and 54 years old, and 1.28∶1 (539∶421) for people over 55 years old. Cases in Ningde City accounted for 30.65% (1 571/5 126) of the total cases. Most hotspots were occurred in Ningde City. Recurrent and clustered cases were found in family members. Conclusions: Typhoid fever was prevalent at a low level in Fujian Province during 2011-2022, indicating that strengthening the prevention and control measures should target key areas and populations. The incidence of typhoid fever in Fujian Province showed spatial aggregation phenomenon, and most cases gathered in Ningde City. Intensive study for the influencing factors of spatial clustering should be conducted.

HCV-induced autophagy and innate immunity.

The interplay between autophagy and host innate immunity has been of great interest. Hepatitis C virus (HCV) impedes signaling pathways initiated by pattern-recognition receptors (PRRs) that recognize pathogens-associated molecular patterns (PAMPs). Autophagy, a cellular catabolic process, delivers damaged organelles and protein aggregates to lysosomes for degradation and recycling. Autophagy is also an innate immune response of cells to trap pathogens in membrane vesicles for removal. However, HCV controls the autophagic pathway and uses autophagic membranes to enhance its replication. Mitophagy, a selective autophagy targeting mitochondria, alters the dynamics and metabolism of mitochondria, which play important roles in host antiviral responses. HCV also alters mitochondrial dynamics and promotes mitophagy to prevent premature cell death and attenuate the interferon (IFN) response. In addition, the dysregulation of the inflammasomal response by HCV leads to IFN resistance and immune tolerance. These immune evasion properties of HCV allow HCV to successfully replicate and persist in its host cells. In this article, we discuss HCV-induced autophagy/mitophagy and its associated immunological responses and provide a review of our current understanding of how these processes are regulated in HCV-infected cells.

[Effects of ppk1 deletion on the drug susceptibility of uropathogenic Escherichia coli producing ESBLs].

To investigate the effect and the mechanism of ppk1 gene deletion on the drug susceptibility of uropathogenic Escherichia coli producing extended-spectrum beta-lactamases (ESBLs-UPEC). The study was an experimental study. From March to April 2021, a strain of ESBLs-UPEC (genotype was TEM combined with CTX-M-14) named as UE210113, was isolated from urine sample of the patient with urinary tract infection in the Laboratory Department of Guangzhou Eighth People's Hospital, meanwhile its ppk1 gene knock-out strain Δpk1 and complemented strain Δpk1-C were constructed by suicide plasmid homologous recombination technique, which was used to study the effect of ppk1 gene on ESBLs-UPEC drug sensitivity and its mechanism. The drug susceptibility of UE210113, Δpk1, and Δpk1-C were measured by Vitek2 Compact System and broth microdilution method. The quantitative expression of ESBLs, outer membrane protein and multidrug efflux systems encoding genes of UE210113, Δpk1 and Δpk1-C were performed by using qRT-PCR analysis. By using two independent sample Mann-Whitney U test, the drug susceptibility results showed that, compared with UE210113 strain, the sensitivities of Δpk1 to ceftazidime, cefepime, tobramycin, minocycline and cotrimoxazole were enhanced (Z=-2.121,P<0.05;Z=-2.236,P<0.05;Z=-2.236,P<0.05;Z=-2.121,P<0.05), and the drug susceptibility of Δpk1-C restored to the same as which of UE210113 (Z=0,P>0.05). The expression levels of ESBLs-enconding genes blaTEM and blaCTX-M-14 in Δpk1 were significantly down-regulated compared with UE210113, but the expression was not restored in Δpk1-C. The expression of outer membrane protein gene omp F in Δpk1 was significantly up-regulated, while the expression of omp A and omp C were down-regulated. The results showed that the expression of multidrug efflux systems encoding genes tol C, mdt A and mdtG were down-regulated in Δpk1 compared with UE210113. The expression of all of the outer membrane protein genes and the multidrug efflux systems genes were restored in Δpk1-C. In conclusion,the lost of ppk1 gene can affect the expression of the outer membrane protein and multidrug efflux systems encoding genes of ESBLs-UPEC, which increase the sensitivity of ESBLs-UPEC to various drugs.

Ultrasonic bone curette in thoracic spinal decompression: a comprehensive systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to compare the efficacy and safety of ultrasonic bone curette (UBC) and conventional surgical instruments in thoracic laminectomy decompression (TLD) for the treatment of thoracic spinal stenosis (TSS) by meta-analysis. MATERIALS AND METHODS: Two authors independently searched Medline via PubMed, Embase, Cochrane Library, Web of Science, Wanfang Database, and China National Knowledge Infrastructure for the period from the establishment of the database until January 2023 to identify the studies on the safety and efficacy of UBC vs. conventional instruments for TSS. Data extraction and quality assessment were performed by two researchers independently. We used RevMan 5.4 software (Review Manager Web, The Cochrane Collaboration, Copenhagen, Denmark) to analyze the data. RESULTS: Eight retrospective studies were included in the present work. This meta-analysis revealed that no significant differences in the preoperative JOA scores, the JOA scores at the last follow-up, the improvement rate of JOA scores, and the incidence of cerebrospinal fluid leakage/dura injury were detected between the two groups (p>0.05). However, there were significant differences in the operative time and intraoperative blood loss during single-level TLD [operative time: MD=-1.47, 95% CI (-1.86, -1.09), p<0.001; intraoperative blood loss: MD=-46.62, 95% CI (-53.83, -39.40), p<0.001], total operative time [MD=-56.88, 95% CI (-69.66, -44.10), p<0.001], total intraoperative blood loss [MD=-143.52, 95% CI (-212.49, -74.54), p<0.001], the incidence of neurological deterioration/nerve root injury [RR= 0.29, 95% CI (0.09, 0.91), p=0.03] between the groups. CONCLUSIONS: The application of UBC in TLD to treat TSS is safe and effective. UBC can significantly shorten operation time and reduce intraoperative blood loss compared to traditional surgical instruments. Moreover, it has the advantage of reducing perioperative nerve injury.

[A monogenic lupus family caused by homozygous deletions of DNASE1L3 gene and literature review].

Objective: To report the clinical features and genetic variations of monogenic lupus caused by DNASE1L3 deficiency and to introduce preliminary experience on diagnosis and treatment for this disease. Methods: Clinical data of 3 children from the same pedigree were collected who were diagnosed with DNASE1L3 defect-associated monogenic lupus in August 2020 by Department of Pediatrics, Peking Union Medical College Hospital referred from Department of Pediatrics, Boai Hospital of Zhongshan. DNA was extracted from the peripheral blood of the patients and their parients to perform genetic analysis and confirmation. Six interferon-stimulated genes were relatively quantified to examine the activation of the type I interferon signaling. "DNASE1L3" "systemic lupus erythematosus" and "SLE" were searched in PubMed, Wangfang Data, CNKI databases for related reports from database established date to June 2022. Spectrum of genetic variations and clinical phenotypes were analyzed in combination with this pedigree. Results: Case 1, a 14-year-old girl with edema, hematuria, and heavy proteinuria, presented with membranous nephropathy. Case 2, the 12-year-old younger brother of case 1 with hematologic, cardiac, pulmonary, renal involvement, positive antinuclear antibody, positive anti-double-stranded DNA antibody and low complement C3, manifested with systemic lupus erythematosus. Case 3, the 8-year-old younger sister of case 1 with hematologic, cardiac, pulmonary and renal involvement, positive antinuclear antibody, positive anti-double-stranded DNA antibody, and low complement C3 and C4, manifested with systemic lupus erythematosus. Genetic testing revealed that all 3 patients carried homozygous deletions in exons 3 and 4 on DNASE1L3 gene. Interferon scores were elevated in case 1, 2 and their parents but normal in case 3. All 3 patients were diagnosed with monogenic lupus caused by DNASE1L3 defects. Literature searching identified 10 relevant publications in English and 0 publication in Chinese, involving 42 patients from 18 pedigrees (including the 3 cases from this pedigree). Nine variants were found: c.289_290delAC (p.T97Ifs*2), c.643delT (p.W215Gfs*2), c.320+4delAGTA, c.321-1G>A, Ex5 del, c.433G>A, c.581G>A (p.C194Y), c.537G>A (p.W179X), and Ex3-4 del. The hotspot variants were c.643delT (43% (36/84)) and c.289_290delAC (36% (30/84)). Kidney was affected in 31 cases (74%) of the 42 cases. Among the 25 patients, joints were affected in 16 cases (64%), fever were reported in 13 cases (52%) hematologic system was involved 13 cases (52%), rash was present in 10 cases (40%), intestinal tract was involved in 8 cases (32%), lungs were involved in 6 cases (24%), eyes were involved in 4 cases (16%), and the heart was involved in 4 cases (16%). The 2 cardiopulmonary affected patients from literature showed poor prognosis, with 1 died, and 1 right heart failure. Conclusions: The clinical manifestations of monogenic lupus caused by DNASE1L3 defect are highly heterogenous, primarily with renal, blood, joint, intestinal, and cardiopulmonary involvement. There is no correlation between the genotype and the phenotype. DNASE1L3 defects were predominantly mediated by null varations including nonsense, splicing, frameshift and exon deletions. The hotspot variants are c.643delT and c.289_290delAC. DNASE1L3 defects should be cautioned in early-onset lupus-like patients with renal, joint and hematologic involvement. Cardiopulmonary involved patients require close monitoring for poor prognosis. Copy number variations should be carefully analyzed after negative whole exome sequencing.

[Effects and mechanism of water-soluble chitosan hydrogel on infected full-thickness skin defect wounds in diabetic mice].

Objective: To explore the effects and mechanism of water-soluble chitosan hydrogel on infected full-thickness skin defect wounds in diabetic mice. Methods: The experimental research method was adopted. The control hydrogel composed of polyvinyl alcohol and gelatin, and the water-soluble chitosan hydrogel composed of the aforementioned two materials and water-soluble chitosan were prepared by the cyclic freeze-thaw method. The fluidity of the two dressings in test tube before and after the first freeze-thawing was generally observed, and the difference in appearance of the final state of two dressings in 12-well plates were compared. According to random number table (the same grouping method below), the cell strains of L929 and HaCaT were both divided into water-soluble chitosan hydrogel group and control hydrogel group, respectively. After adding corresponding dressings and culturing for 24 h, the cell proliferation activity was measured using cell counting kit 8. Rabbit blood erythrocyte suspensions were divided into normal saline group, polyethylene glycol octyl phenyl ether (Triton X-100) group, water-soluble chitosan hydrogel group, and control hydrogel group, which were treated accordingly and incubated for 1 hour, and then the hemolysis degree of erythrocyte was detected by a microplate reader. Twenty-four female db/db mice aged 11-14 weeks were selected, and full-thickness skin defect wounds on their backs were inflicted and inoculated with the methicillin-resistant Staphylococcus aureus (MRSA), 72 h later, the mice were divided into blank control group, sulfadiazine silver hydrogel group, control hydrogel group, and water-soluble chitosan hydrogel group, which were treated accordingly. On post injury day (PID) 0 (immediately), 7, 14, and 21, the healing of the wound was observed. On PID 14 and 21, the wound healing rate was calculated. On PID 14, MRSA concentration in wounds was determined. On PID 21, the wounds were histologically analyzed by hematoxylin and eosin staining; the expression of CD31 in the wounds was detected by immunofluorescence method, and its positive percentage was calculated. Raw264.7 cells were taken and divided into interleukin-4 (IL-4) group, blank control group, control hydrogel group, and water-soluble chitosan hydrogel group, which were treated accordingly. At 48 h of culture, the percentages of CD206 positive cells were detected by flow cytometry. The number of samples was all 3. Data were statistically analyzed with independent sample t test, one-way analysis of variance, analysis of variance for repeated measurement, least significant difference test, and Dunnett T3 test. Results: Two dressings in test tube had certain fluidity before freeze-thawing and formed semi-solid gels after freeze-thawing for once. The final forms of two dressings in 12-well plates were basically stable and translucent sheets, with little difference in transparency. At 24 h of culture, the cell proliferation activities of L929 and HaCaT in water-soluble chitosan hydrogel group were significantly higher than those in control hydrogel group (with t values of 6.37 and 7.50, respectively, P<0.01). At 1 h of incubation, the hemolysis degree of erythrocyte in water-soluble chitosan hydrogel group was significantly lower than that in Triton X-100 group (P<0.01), but similar to that in normal saline group and control hydrogel group (P>0.05). On PID 0, the traumatic conditions of mice in the 4 groups were similar. On PID 7, more yellowish exudates were observed inside the wound in blank control group and control hydrogel group, while a small amount of exudates were observed in the wound in sulfadiazine silver hydrogel group and water-soluble chitosan hydrogel group. On PID 14, the wounds in blank control group and control hydrogel group were dry and crusted without obvious epithelial coverage; in sulfadiazine silver hydrogel group, the scabs fell off and purulent exudate was visible on the wound; in water-soluble chitosan hydrogel group, the base of wound was light red and obvious epithelial coverage could be observed on the wound. On PID 14, the wound healing rate in water-soluble chitosan hydrogel group was significantly higher than that in the other 3 groups (all P<0.01). On PID 21, the wound in water-soluble chitosan hydrogel group was completely closed, while the wounds in the other 3 groups were not completely healed; the wound healing rate in water-soluble chitosan hydrogel group was significantly higher than that in the other 3 groups (all P<0.01). On PID 14, the concentration of MRSA in the wound in water-soluble chitosan hydrogel group was significantly lower than that in blank control group (P<0.01), but similar to that in control hydrogel group and sulfadiazine silver hydrogel group (P>0.05). On PID 21, the new epidermis was severely damaged in blank control group; the epidermis on the wound in control hydrogel group also had a large area of defect; complete new epidermis had not yet being formed on the wound in sulfadiazine silver hydrogel group; the wound in water-soluble chitosan hydrogel group was not only completely covered by the new epidermis, the basal cells of the new epidermis were also regularly aligned. On PID 21, the percentage of CD31 positivity in the wound in water-soluble chitosan hydrogel group was (2.19±0.35)%, which was significantly higher than (0.18±0.05)% in blank control group, (0.23±0.06)% in control hydrogel group, and (0.62±0.25)% in sulfadiazine silver hydrogel group, all P<0.01. At 48 h of culture, the percentage of CD206 positive Raw264.7 cells in water-soluble chitosan hydrogel group was lower than that in IL-4 group (P>0.01) but significantly higher than that in blank control group and control hydrogel group (P<0.05 or P<0.01). Conclusions: The water-soluble chitosan hydrogel has good biosafety and can induce higher level of macrophage M2 polarization than control hydrogel without water-soluble chitosan, so it can enhance the repair effect of MRSA-infected full-thickness skin defect wounds in diabetic mice and promote rapid wound healing.

Effects of treatment processes on AOC removal and changes of bacterial diversity in a water treatment plant.

The effectiveness of different treatment processes on assimilable organic carbon (AOC) removal and bacterial diversity variations was evaluated in a water treatment plant. The van der Kooij technique was applied for AOC analysis and responses of bacterial communities were characterized by the metagenomics assay. Results show that the AOC concentrations were about 93, 148, 43, 51, 37, and 38 µg acetate-C/L in effluents of raw water basin, preozonation, rapid sand filtration (RSF), ozonation, biofiltration [biological activated carbon (BAC) filtration], and chlorination (clear water), respectively. Increased AOC concentrations were observed after preozonation, ozonation, and chlorination units due to the production of biodegradable organic matters after the oxidation processes. Results indicate that the oxidation processes were the main causes of AOC formation, which resulted in significant increases in AOC concentrations (18-59% increment). The AOC removal efficiencies were 47, 28, and 60% in the RSF, biofiltration, and the whole system, respectively. RSF and biofiltration were responsible for the AOC treatment and both processes played key roles in AOC removal. Thus, both RSF and biofiltration processes would contribute to AOC treatment after oxidation. Sediments from the raw water basin and filter samples from RSF and BAC units were collected and analyzed for bacterial communities. Results from scanning electron microscope analysis indicate that bacterial colonization was observed in filter materials. This indicates that the surfaces of the filter materials were beneficial to bacterial growth and AOC removal via the adsorption and biodegradation mechanisms. Next generation sequencing analyses demonstrate that water treatment processes resulted in the changes of bacterial diversity and community profiles in filters of RSF and BAC. According to the findings of bacterial composition and interactions, the dominant bacterial phyla were Proteobacteria (41% in RSF and 56% in BAC) followed by Planctomycetes and Acidobacteria in RSF and BAC systems, which might affect the AOC biodegradation efficiency. Results would be useful in developing AOC treatment and management processes in water treatment plants.

[Analysis on repetitive reporting of hepatitis B in Fujian province, 2016-2020].

Objective: To analyze the repetitive reporting of hepatitis B in Fujian province during 2016-2020, and provide evidence for the improvement of hepatitis B surveillance. Methods: The reporting cards from the China Information System for Disease Control and Prevention were collected and divided into repetitive reporting cards and non-repetitive reporting cards from the report cards collected according to the valid ID number on the cards, and the proportion of repetitive report cards and related factors were analyzed by using software SAS 9.4. Results: A total of 314 551 hepatitis B reporting cards were submitted in Fujian from 2016 to 2020, in which 90.93% (286 020/314 551) were included in the analysis. The repetitive reporting cards accounted for 10.48% (29 982/286 020). The annual proportion of the repetitive reporting cards from 2016 to 2020 was between 2.98% and 3.71%, showing an overall increasing trend year by year (Z=2.26, P=0.024). The proportions of the repetitive reporting cards in 1-5 years were 3.17%, 5.40%, 7.74%, 9.27% and 10.48%, respectively, showing an increase trend with year (Z=128.16, P<0.001). The proportions of the repetitive reporting cards in 10 areas of Fujian ranged from 5.44% to 13.48% with significant difference (χ2=2 050.41, P<0.001) and increased with the increase of reported incidence of hepatitis B (Z=26.92, P<0.001). There were significant differences in relationships between repetitive reporting proportion and sex, age and type of the cases between the areas with high incidence and low incidence of hepatitis B. Conclusions: The reported incidence of hepatitis B was seriously affected by the repetitive reporting in Fujian from 2016 to 2020. A cross-year and cross-area surveillance mechanism for hepatitis B should be established and targeted measures should be taken to strengthen the control of the repetitive reporting and improve the surveillance for hepatitis B.

[The diagnostic value of whole blood Epstein-Barr virus DNA load in lymphoproliferative diseases after allogeneic hematopoietic stem cell transplantation].

Objectives: To investigate the diagnostic value of whole blood quantitative PCR for DNA load of Epstein-Barr virus (EBV) in post-transplant lymphoproliferative disease (PTLD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: A total of 694 patients with hematologic diseases who underwent allo-HSCT at the Hematology Department of Peking University First Hospital from April 2004 to April 2019 were included, and their data were retrospectively analyzed. Results: ①Among the 694 cases, 29 cases (22 males and 7 females, with a median age of 22 (1-52) years) developed PTLD after allo-HSCT with a cumulative incidence of 4.2% and a median onset time of 2.1 (0.8-20.6) months. ② Univariate analysis showed that age<30 years, diagnosis with aplastic anemia, human leukocyte antigen (HLA) mismatch, use of antithymocyte globulin (ATG) in preconditioning regimens, and EBV reactivation were the risk factors for the occurrence of PTLD. Multivariate analysis showed that EBV reactivation was an independent risk factor for the occurrence of PTLD. ③Further analysis of EBV reactivation cases showed that the peak value of EBV-DNA load was significantly higher in the PTLD group than that in the non-PTLD group (P<0.001) and the incidence of PTLD increased with the increase of EBV-DNA load. Receiver operating characteristic (ROC) curve analysis indicated that PTLD was more likely to be diagnosed when the EBV-DNA load was >1.19×10(6) copies/ml (sensitivity 0.800 and specificity 0.768) . ④All patients with PTLD received rituximab-based treatment, with an overall response rate of 86.2% and an overall survival rate of 54.3%. Conclusion: The PTLD occurrence after allo-HSCT is highly correlated with EBV reactivation, and the higher the EBV-DNA load, the greater the risk of PTLD occurrence. The dynamic monitoring of EBV-DNA load plays an important role in predicting PTLD occurrence.

[Application value of urinary IGFBP7 and TIMP-2 in acute kidney injury with decompensated hepatitis B virus-related liver cirrhosis].

Objective: To investigate the application value of new urinary biomarkers insulin-like growth factor binding protein 7 (IGFBP7) and tissue matrix metalloproteinase inhibitor-2 (TIMP-2) in acute kidney injury with decompensated hepatitis B virus-related liver cirrhosis. Methods: 45 newly hospitalized cases with decompensated hepatitis B virus-related liver cirrhosis were selected. Among them, 19 cases were combined with AKI on admission (cirrhosis-AKI group), 26 cases without AKI (cirrhosis-non-AKI group), and 12 healthy cases (normal control group). First-morning urine samples were collected and IGFBP7 and TIMP-2 were detected by enzyme-linked immunosorbent assay (ELISA). Urinary IGFBP7 and serum creatinine (SCr) were dynamically monitored after hospitalization in cirrhosis-non-AKI group. Normally distributed measurement data were compared by t-test, and non-normally distributed measurement data were compared by rank sum test. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic accuracy of the indicators. Results: Urinary IGFBP7, IGFBP7 with TIMP-2 (IGFBP7×TIMP-2) in cirrhosis-AKI group (n = 19) were equally higher than that of the cirrhosis-non-AKI group (P < 0.05). Urinary IGFBP7, TIMP-2 and IGFBP7×TIMP-2 in cirrhosis-AKI group or cirrhosis-non-AKI group were significantly higher than those of the normal control group (P < 0.01). The AUC of urinary IGFBP7 and urinary IGFBP7×TIMP-2 for diagnosis of AKI were 0.703 (95% CI 0.547-0.860) and 0.700 (95% CI 0.541-0.859), respectively. In the liver cirrhosis-non-AKI group (n = 26), 5 cases of AKI were newly diagnosed according to the changes in SCr during hospitalization (progressive group). Urinary IGFBP7 was significantly increased 2 days before the diagnosis of AKI. The concentration of urinary IGFBP7 at admission in the progressive group (n = 5) was higher than that of the non-progressive group (n = 21) (P < 0.05). Conclusion: Urinary IGFBP7 and TIMP-2 concentrations were significantly increased in patients with decompensated hepatitis B virus-related liver cirrhosis. When AKI occurred, urinary IGFBP7 and IGFBP7×TIMP-2 was further increased. Urinary IGFBP7 is valuable for early AKI diagnosis, and may play a role in predicting AKI occurrence.

Let-7 derived from endometrial extracellular vesicles is an important inducer of embryonic diapause in mice.

Embryonic diapause is a maternally controlled phenomenon. The molecule controlling the onset of the phenomenon is unknown. We demonstrated that overexpression of microRNA let-7a or incubation with let-7g-enriched extracellular vesicles from endometrial epithelial cells prolonged the in vitro survival of mouse blastocysts, which developed into live pups after having been transferred to foster mothers. Similar to in vivo dormant blastocysts, let-7-induced dormant blastocysts exhibited low level of proliferation, apoptosis, and nutrient metabolism. Let-7 suppressed c-myc/mTORC1 and mTORC2 signaling to induce embryonic diapause. It also inhibited ODC1 expression reducing biosynthesis of polyamines, which are known to reactivate dormant embryos. Furthermore, the overexpression of let-7 blocked trophoblast differentiation and implantation potential of human embryo surrogates, and prolonged survival of human blastocysts in vitro, supporting the idea that embryonic diapause was an evolutionary conserved phenomenon. In conclusion, let-7 is the main factor inducing embryonic diapause.

The global transcriptomic signature in sinonasal tissues reveals roles for tissue type and chronic rhinosinusitis disease phenotype.

BACKGROUND: RNA sequencing (RNA-Seq) allows the characterization of a global transcriptomic signature in a least-biased fashion, but few studies have applied this method to investigate the pathophysiology of CRS. METHODS: We collected mucosal tissue samples from 6 CRS without nasal polyps (CRSsNP), 6 CRS with nasal polyps (CRSwNP), and 6 control patients. Additional matched polyp samples were collected from the 6 CRSwNP patients. RNA was extracted and sequenced on the Illumina HiSeq-2500. Differential gene expression and pathway analyses were performed. RESULTS: CRSsNP showed evidence of upregulated interferon-mediated immunity, MHC-class-I mediated antigen presentation, CXCR3 binding, neutrophil chemotaxis and degranulation, and potential downregulation of genes related to cilia movement and production. CRSwNP polyp tissue showed upregulation of B-cell mediated immune responses, but reduced expression of genes related to epithelial morphogenesis and haemostasis. Polyps also showed a generalized reduction of positive gene regulation. The sinonasal transcriptomic signature was largely determined by tissue type (polyp versus mucosa) and disease phenotype, with minimal signal originating from the individual patient. CONCLUSION: RNA-Seq is a useful tool to explore the complex pathophysiology of CRS. Our findings stress the importance of tissue selection in molecular research utilizing sinonasal tissue, and demonstrate the limitation of the sNP/wNP paradigm (and the importance of endotyping). On the other hand, classical CRSsNP/wNP disease phenotypes played some role in determining the global transcriptomic signature, and should not be hastily discarded. The value of RNA-Seq-described transcriptomic signatures in exploring endotypes is yet to be explored in future studies.

lncRNA CASC2 suppresses the growth of hemangioma cells by regulating miR-18a-5p/FBXL3 axis.

Dysregulation of lncRNA cancer susceptibility candidate 2 (CASC2) is involved in the pathogenesis of multiple malignancies. However, the underlying mechanisms by which lncRNA CASC2 regulates the proliferation of hemangiomas (HAs) remain undocumented. Herein, the expression levels of lncRNA CASC2 and VEGF in proliferating or involuting phase HAs were assessed by qRT-PCR analysis, and the effects of lncRNA CASC2 on HAs cell growth were evaluated by MTT, colony formation assays and Western blot analysis. lncRNA CASC2 specific binding with miR-18a-5p was confirmed by luciferase report assay. Consequently, we found that the expression of lncRNA CASC2 was reduced in proliferating phase HAs as compared with the involuting phase HAs or normal tissues, and possessed a negative correlation with VEGF expression in proliferating phase HAs. Restored expression of lncRNA CASC2 repressed cell viability and colony formation and downregulated VEGF expression, while silencing lncRNA CASC2 showed the opposite effects. Moreover, lncRNA CASC2 was confirmed to bind with miR-18a-5p, which could reverse lncRNA CASC2-induced anti-proliferative effects by targeting FBXL3 in HAs cells. Altogether, our findings demonstrated that lncRNA CASC2 suppressed the growth of HAs cells by regulating miR-18a-5p/FBXL3 axis.

Predicting gastro-oesophageal variceal bleeding in hepatitis B-related cirrhosis by CT radiomics signature.

AIM: To develop liver a computed tomography (CT) radiomics model to predict gastro-oesophageal variceal bleeding (GVB) secondary to hepatitis B-related cirrhosis. MATERIALS AND METHODS: Electronic medical records and image data of liver triple-phase contrast-enhanced CT examinations of 295 patients with hepatitis B-related cirrhosis were collected retrospectively from two hospitals. Two hundred and thirty-six and 59 patients were enrolled randomly into the training and validation cohorts, respectively; and 75 in the training cohort and 16 in the validation cohort endured GVB while the others did not during follow-up period. Radiomics features of the liver were extracted from the portal venous phase images, and clinical features came from medical records. The tree-based method and univariate feature selection were used to select useful features. The radiomics model, clinical model, and integration of radiomics and clinical models were built using the useful image features and/or clinical features. Predicting performance of three models was evaluated with the area under receiver-operating characteristic curve (AUC), accuracy, and F-1 score. RESULTS: Twenty-one useful radiomics features and/or three clinical features were selected to build prediction models that correlated with GVB. AUC of integration of radiomics and clinical models was larger than of clinical or radiomics models for the training cohort (0.83±0.09 versus 0.64±0.08 or 0.82±0.10) and the validation cohort (0.64 versus 0.61 or 0.61). Integration of radiomics and clinical models obtained good performance in predicting GVB for both the training and validation cohorts (accuracy: 0.76±0.07 and 0.73, and F-1 score: 0.77±0.09 and 0.72, respectively). CONCLUSION: Integration of the radiomics and clinical models may be a non-invasive method to predict GVB.

[Analysis on association between incidence of hand foot and mouth disease and meteorological factors in Xiamen, 2013-2017].

Objective: To study the influence of meteorological factors on the incidence of hand foot and mouth disease (HFMD) in Xiamen, Fujian province, and provide scientific evidence for the early warning, prediction, prevention and control of HFMD. Methods: Correlation analysis and distribution lag nonlinear models (DLNM) analysis of meteorological factors such as daily average pressure, daily average relative humidity, daily average temperature and sunshine hours and the incidence of HFMD in Xiamen during 2013 to 2017 were conducted by using R3.4.3 software. Results: A total of 36 464 cases of HFMD were reported in Xiamen during 2013-2017, and the incidence showed an upward trend (F=40.359, P=0.008). The daily average relative humidity, daily average temperature and sunshine hours were positively correlated with the incidence of HFMD (r>0), and the daily average site pressure was negatively correlated with the incidence of HFMD (r<0). In the case of a lag of 0-5 days, when the daily average pressure of the station was higher than 1 005 hPa, the risk of HFMD gradually increased with the increase of air pressure, and the risk of disease decreased with the increase of lag days. The risk was highest when air pressure was 1 017 hPa and at the lag of 0 day (RR=1.14, 95%CI: 0.67-1.94). When the relative humidity was higher than 95%, the risk of HFMD gradually increased with the increase of relative humidity, and the lag time ranged from 0 day to 10 days, which was most obvious on the 4(th) and 5(th) days. The risk was highest when relative humidity was 100% and at the lag of 5 days (RR=1.32, 95%CI: 1.02-1.71). When the air temperature was >28 ℃ and <8 ℃, the risk of HFMD existed, but the lag time was inconsistent. The relative risk was highest during 15-20 days at low air temperature, and the lag time at high air temperature was mainly during 5-15 days. The risk was highest when air temperature was 28 ℃ and at the lag of 4 days (RR=1.10, 95%CI: 0.94-1.29). The sunshine time was >12 h and lag of 0-3 days was a risk factor for the incidence of HFMD. The risk was highest when sunshine time was 13 h and the lag of 0 day (RR=1.20, 95%CI: 1.05-1.36). Conclusion: Meteorological factors such as daily average pressure, daily average relative humidity, daily average temperature and sunshine hours were associated with the incidence of HFMD with certain lag in Xiamen. So, it is suggested to use these data in the early warning system of HFMD.