[Porphyromonas gingivalis persisters induce the immuno-inflammatory responses in macrophages by upregulating the forkhead box1 signaling pathway].

Objective: To investigate the effects of Porphyromonas gingivalis (Pg) persisters (Ps) on immuno-inflammatory responses in macrophages, and to explore the underlying mechanisms. Methods: Pg cells were cultured to the stationary phase (72 h), and subsequently treated by high concentration of metronidazole at 100 mg/L, amoxicillin at 100 mg/L and the combination of them for different time period, named as metronidazole group, amoxicillin group and (metronidazole+amoxicillin) group. Pg cells without management were used as blank control. The survival profile of PgPs cells was measured by colony-forming unit assay. The living state of PgPs was observed by Live/Dead staining. Then, Pg and metronidazole-treated PgPs (M-PgPs) were used to treat macrophages, named as Pg group and M-PgPs group. Transmission electron microscopy (TEM) was used to observe the bacteria in the macrophages. The expression levels of proinflammatory cytokines in macrophages were determined by real-time fluorescence quantitative PCR and enzyme-linked immunosorbent assay. The location of forkhead box 1 (FOXO1) was detected by confocal immunofluorescence microscopy. After inhibiting or enhancing the FOXO1 expressions using inhibitors (Fi) or activators (Fa) respectively, the macrophages were treated with Pg and M-PgPs, divided as Blank group, Pg group, M-PgPs group, Fi group, (Fi+Pg) group, (Fi+M-PgPs) group, Fa group, (Fa+Pg) group and (Fa+M-PgPs) group. Then, the expression pattens of proinflammatory cytokines were assessed. Results: Remarkable number of lived PgPs was observed, both in planktonic culture and Pg biofilms either treated with metronidazole, amoxicillin or both, and those persisters could form new colonies. Pg and M-PgPs were able to enter into the macrophages and the protein expression levels of interleukin (IL)-1ß, IL-6, IL-8 and tumor necrosis factor-α (TNF-α) [Pg group: (2 392±188), (162±29), (5 558±661), (789±155) µg/L; M-PgPs group: (2 415±420), (155±3), (5 732±782), (821±176) µg/L)] were significantly upregulated than those in Blank group [(485±140), (21±9), (2 332±87), (77±7) µg/L] (P<0.01). Moreover, Pg and M-PgPs could facilitate the nuclear translocation and accumulation of FOXO1. In addition, the relative mRNA expression levels of FOXO1, BCL6 and KLF2 were upregulated when compared to Blank group (P<0.05). Furthermore, the protein expression levels of IL-1ß, IL-6, IL-8 and TNF-α in Fi+Pg group [(1 081±168), (70±8), (1 976±544), (420±47) µg/L] were remarkably lower than Pg group [(4 411±137), (179±6), (5 161±929), (934±24) µg/L] (P<0.05). Similarly, the protein expression levels of IL-1ß, IL-6, IL-8 and TNF-α in Fi+M-PgPs group [(1 032±237), (74±10), (1 861±614), (405±32) µg/L] were remarkably lower than M-PgPs group [(4 342±314), (164±17), (4 438±1 374), (957±25) µg/L] (P<0.05). On the contrary, the protein expression levels of IL-1ß, IL-6, IL-8 and TNF-α in Fa+Pg group [(8 198±1 825), (431±28), (8 919±650), (2 186±301) µg/L] and Fa+M-PgPs group [(8 159±2 627), (475±26), (8 995±653), (2 255±387 µg/L) were both significantly higher than Pg group and M-PgPs group, respectively (P<0.05). Conclusions: PgPs are highly tolerant to metronidazole and amoxicillin. The M-PgPs could enhance the immuno-inflammatory responses in macrophages by upregulating the FOXO1 signaling pathway, while this effect exhibits no significant difference with Pg.

Author Correction: Phase I study of the pharmacokinetics and safety of single and multiple doses of intravenous N-acetylcysteine in healthy Chinese subjects.

Eur Rev Med Pharmacol Sci 2023; 27 (24): 12103-12111-DOI: 10.26355/eurrev_202312_34808-PMID: 38164872, published online on December 22, 2023. After publication, the authors found that Table III's legend was the same as that of Table II. Therefore, Table III's legend has been corrected as follows: Table III. Plasma PK parameters following repeat doses of IV NAC 600 mg (n = 24). There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34808.

[Pedigree Analysis and Molecular Mechanism Study of Hereditary Glanzmann Thrombasthenia Caused by Compound Heterozygous Mutation of the ITGA2B Gene].

Objective: The phenotype and genotype of a pedigree with Glanzmann thrombasthenia caused by compound heterozygous mutation in the ITGA2B gene and its molecular pathogenesis were explored. Methods: The platelet aggregation rate of the proband and his family was detected by using a platelet aggregation test with adenosine diphosphate, collagen, epinephrine, arachidonic acid, and ristocetin. The expression levels of CD41 (αⅡb), CD61 (ß3), and CD42b (GPⅠb) on the platelet surface was detected by flow cytometry. Gene sequencing technology was used for the genetic identification of the family. RT-PCR was used in the detection of mRNA splicing, and qRT-PCR was used in detecting the relative mRNA level of the ITGA2B gene. Bioinformatics analysis was used to evaluate the pathogenicity of mutation sites and their effects on protein structure and function. The expressions of total αⅡb and ß3 in platelets were analyzed by Western blot. Results: Except ristocetin, the other four inducers could not induce platelet aggregation in the proband. Flow cytometry showed that the expression levels of αⅡb and ß3 were only 0.25% and 9.76%, respectively, on the platelet surface of the proband, whereas GPⅠb expression was relatively normal. The expression levels of glycoproteins in the other family members were almost normal. c.480C>G and c.2929C>T mutations were detected in the proband through gene sequencing. The c.480C>G mutation was inherited from his mother, and the c.2929C>T mutation was inherited from his father. The RT-PCR and sequencing results showed that the c.480C>G mutation caused mRNA splicing in the proband and his mother, resulting in the deletion of 99 bases in c.476G-574A (p.S160-S192). qRT-PCR showed that the c.2929C>T variant reduced the mRNA level of the ITGA2B gene in the proband and his father. Bioinformatics analysis suggested that the c.480C>G mutation might form a binding sequence with hnRNP A1 protein and generate the 5'SS splice site. The three-dimensional structural model of the αⅡb subunit showed that the ß-propeller domain of the p.S160-S192 deletion lost two ß-strands and one α-helix in blade 2. The c.2929C>T nonsense mutation caused premature translation termination and produced a truncated protein with the deletion of p.R977-E1039, including the cytoplasmic domain, transmembrane domain, and a ß chain of the extracellular Calf-2 domain. The total αⅡb expression of the proband was absent, and the relative expression of ß3 was 11.36% of the normal level. Conclusion: The compound heterozygous mutation c.480C>G in exon 4 and c.2929C>T in exon 28 of the ITGA2B gene probably underlies Glanzmann thrombasthenia in this pedigree.

[Effects of polyphyllin â ¦ on proliferation, apoptosis and cell cycle of diffuse large B-cell lymphoma cells].

The aim of this study was to investigate the effects of polyphyllin Ⅶ (PP Ⅶ) on proliferation, apoptosis, and cell cycle of diffuse large B-cell lymphoma (PLBCL) cell lines U2932 and SUDHL-4. The DLBCL cell lines were divided into a control group and a PPⅦ group, and experiments were conducted using MTT assay, flow cytometry, and Western blotting.Results showed that compared with the control group, PPⅦ significantly inhibited the proliferation of U2932 and SUDHL-4 cells (P<0.05). Apoptosis assays demonstrated that treatment with 0.50 and 1.00 µmol/L PP Ⅶ significantly increased the apoptosis rates of both cell lines (P<0.05), upregulated apoptosis-related proteins, and downregulated Bcl-2 protein level (P<0.05). Cell cycle analysis revealed that PPⅦ treatment led to an increase in G0/G1-phase cells (P<0.05) and a decrease in G2/M-phase cells (P<0.05), significantly downregulated cyclin D1, CDK4, CDK6, and survivin protein expression (P<0.05). In conclusion, PPⅦ exerted anti-lymphoma effects by inhibiting proliferation, promoting apoptosis, and inducing G0/G1 phase arrest in DLBCL cells.

[Genotype and epidemiological characteristics of human metapneumovirus among hospitalized cases of acute respiratory infection in children in Changchun City, Jilin Province from 2019 to 2023].

Objective: To investigate the genotype and epidemiological characteristics of human metapneumovirus (HMPV) among hospitalized cases with acute respiratory infections (ARI) in children in Changchun City, Jilin Province, China. Methods: From June 2019 to June 2023, throat swabs of ARI inpatients in Changchun Children's Hospital were collected, and their epidemiological and clinical information were also collected. Quantitative reverse transcription-PCR was used to identify HMPV-positive cases, followed by the amplification of the G gene and genetic analysis in the HMPV-positive cases. Results: A total of 3 311 children hospitalized with ARI were included in this study. Their age ranged from 0 to 17 years old, and the M (Q1, Q3) of age was 2 (1, 3) years. About 1 811 (54.70%) cases were males. A total of 167 HMPV-positive cases were detected with a positive rate of 5.04%, of which 92.81% (155/167) were children under 5 years old. The positive rate of HMPV in 2019 was 6.37% (30/471), which dropped to the lowest in 2020 (2.31%, 10/432). The HMPV-positive rate was then rebounded in 2021 (4.70%, 60/1 277) and 2022 (4.56%, 21/461), which increased to 6.87% (46/670) in 2023. The difference in HMPV-positive rate among each year was statistically significant (P<0.05). The prevalence peak of HMPV varied in different years, showing either a unimodal or bimodal distribution in one year. A total of 79 HMPV G gene sequences were obtained, of which subtype A and subtype B accounted for 48.10% and 51.90%, respectively. All of the subtype A sequences were clarified as A2c duplicated variants, and subtype B was mainly B2 genotype. Besides, subtypes A and B were prevalent alone or co-circulated in different years, and there was a subtype replacement pattern in HMPV. Conclusion: The positive rate of HMPV in hospitalized ARI cases in children is significantly different from 2019 to 2023 in Changchun City. Notably, there are certain switch patterns of HMPV subtypes A and B in different years.

[Clinicopathologic characteristics and survival analysis of primary large B-cell lymphoma of the central nervous system].

Objective: To retrospectively analyze the clinical and pathologic characteristics, response to treatment, survival, and prognosis of patients with primary large B-cell lymphoma of the central nervous system (PCNSLBCL) . Methods: Clinical and pathologic data of 70 patients with PCNSLBCL admitted to Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2010 to November 2022 were collected for retrospective analysis. Survival analysis was performed using the Kaplan-Meier method and log-rank test, and prognosis analysis was conducted using the Cox proportional hazards model. Results: Among 70 patients with PCNSLBCL, complete remission (CRs) were achieved in 49 (70.0% ) and partial remission in 4 (5.7% ) after the first-line induction therapy; the overall remission rate was 75.7%. The 2-year progression-free survival (PFS) rate was 55.8% and the median progression-free survival (mPFS) time was 35.9 months, whereas the 2-year overall survival (OS) rate was 79.1% with a median OS time not reached. After CR induced by first-line therapy, cumulative incidence of relapse (CIR) was lower in patients who had received auto-HSCT than in those who had not received consolidation therapy (P=0.032), whose 2-year PFS rate was 54.4% and mPFS time was 35.9 months; comparatively, the 2-year PFS rate in patients having received oral maintenance of small molecule drugs reached 84.4% with a mPFS time of 79.5 months (P=0.038). Multivariant analysis demonstrated that Class 3 in the Memorial Sloan-Kettering Cancer Center (MSKCC) prognostic model is an independent adverse prognostic factor of OS in patients with PCNSLBCL (HR=3.127, 95% CI 1.057-9.253, P=0.039) . Conclusions: In patients with PCNSLBCL achieving CR after the first-line induction therapy, auto-HSCT as consolidation therapy would lead to a decreased CIR, and PFS time could be prolonged by oral maintenance of small molecule drugs. Class 3 MSKCC prognostic model is independently associated with poorer OS.

[Clinical characteristics and prognostic analysis of 34 patients with primary thyroid lymphoma].

Objective: To investigate the clinical characteristics, diagnosis, treatment, and prognosis of primary thyroid lymphoma (PTL) . Methods: A retrospective analysis was conducted on the clinical and pathological data of 34 newly diagnosed PTL patients admitted to Beijing Tongren Hospital from September 2010 to February 2023. The Kaplan-Meier survival curve and Log-rank test were used for survival analysis, and the Cox regression model was applied for univariate analysis of prognostic factors. Results: All 34 PTL patients presented with cervical mass as the initial clinical manifestation. There were 9 males and 25 females. The pathological diagnosis was diffuse large B-cell lymphoma (DLBCL) in 29 patients and mucosa-associated lymphoid tissue (MALT) lymphoma in 5 patients. Among the DLBCL patients, 6 had B symptoms, 17 had an Eastern Cooperative Oncology Group (ECOG) score of ≥2, the Ann Arbor staging was stage Ⅰ-Ⅱ in 21 cases and stage Ⅲ-Ⅳ in 8 cases, the tumor diameter was ≥10 cm in 4 cases, and 14 had concurrent Hashimoto thyroiditis; 27 cases received chemotherapy, with 21 cases achieving complete remission (CR), 2 cases partial remission (PR), and 6 cases of disease progression; the 5-year progression-free survival and overall survival rates were 78.9% and 77.4%, respectively; univariate survival analysis showed that B symptoms, tumor diameter ≥10 cm, and Ann Arbor stage Ⅲ-Ⅳ were significant factors affecting patient prognosis (P<0.05). MALT lymphoma patients were all in stages Ⅰ-Ⅱ, had an ECOG score of 0-1, and were without B symptoms. All patients underwent surgical resection, with 4 cases achieving CR and 1 case PR. Conclusion: PTL is more common in females with concurrent Hashimoto thyroiditis, with the majority of pathological types being B-cell lymphoma. The main treatment is chemotherapy, supplemented by radiotherapy and surgery, and the prognosis is relatively favorable.

[Characterizing immune microenvironment cell composition of chronic rhinosinusitis with nasal polyps based on mass cytometry technology].

Objective: To analyze the cellular composition characteristics of the nasal tissue immune microenvironment in patients with control, chronic rhinosinusitis without nasal polyps (CRSsNP), non-eosinophilic chronic rhinosinusitis with nasal polyps (neCRSwNP), and eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) using mass cytometry flow technology. Methods: Thirteen CRS patients who underwent endoscopic nasal surgery at the Department of Otorhinolaryngology Head and Neck Surgery of Peking Union Medical College Hospital from March to December 2022 were recruited, including 8 males and 5 females, aged 22.3 to 58.3 years. Three control mucosae were obtained from normal ethmoid or sphenoid sinuses of patients with benign tumors of the temporal fossa or non-functional pituitary adenomas who underwent endoscopic surgery, excluding allergic rhinitis and sinusitis. Sixteen clinical tissue samples (3 of control, 3 of CRSsNP, 4 of neCRSwNP, and 6 of eCRSwNP) were prepared into single-cell suspensions. Mass cytometry flow detection was performed using a combination of 42 molecular markers to analyze the differences in cell subpopulations among the groups. Data were analyzed using GraphPad Prism 9. Results: Based on the mass cytometry flow results, cells from control, CRSsNP, neCRSwNP, and eCRSwNP were divided into seven main cell subgroups, with detailed subgrouping of T/NK cells and myeloid cells. In T/NK cells, compared with the control group, the number of NK CD56bright cells increased in the CRSsNP group, while NK CD56dim cells decreased; compared with the CRSsNP group, the eCRSwNP group showed a decrease in NKT cells and CD4+Tem cells; compared with the CRSsNP group, the eCRSwNP group showed a significant increase in CD25 expression within Treg cells; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in Tbet expression in CD8+Teff cells and CD8+TRM cells; in eCRSwNP, the expression of CD103 in CD8+TRM cells was significantly lower than in CRSsNP. In myeloid cells, compared with the other three groups, the eCRSwNP group showed a significant increase in macrophages and a significant decrease in cDC1 and monocytes; compared with the control group and CRSsNP, the eCRSwNP group also showed a significant decrease in resting state macrophages; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in the level of CX3CR1 within cDC2 and monocytes; the expression levels of NLRP3 in cDC2 and macrophages in the eCRSwNP group were significantly higher than in the other three groups; compared with the control group, the expression levels of Gata3 in cDC2 and macrophages in the eCRSwNP group were also significantly increased; additionally, the expression of CCR2 within monocytes in the eCRSwNP group was lower than in the CRSsNP group. In ILC, compared with the control group, the expression of CCR6 decreased in the eCRSwNP group. Conclusions: Compared with the control group, CRSsNP, and neCRSwNP, eCRSwNP shows an increase in macrophage number, a decrease in cDC1 and resting state macrophages, and depletion of protective cells CD103+CD8+TRM. Additionally, the expression levels of CCR2 and CX3CR1 in monocytes of eCRSwNP are decreased.

Effects of antipsychotics on amino acid levels in patients with first-episode schizophrenia: A prospective study

Background and objectives Alterations in the molecular mechanisms of specific amino acids (AAs) may be implicated in the pathophysiology of schizophrenia (SZ). However, little is known about antipsychotic drugs influence on levels of AAs. This study aimed to further explore antipsychotics' effects on AAs and serum lipid levels in first-episode SZ. Methods Eighty subjects with the International Classification of Diseases, Tenth Edition (ICD-10) criteria-defined SZ were enrolled. The levels of 31 AAs were measured in plasma samples using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results Ten AAs (i.e., citrulline, sarcosine, tyrosine, leucine, proline, hydroxyproline, kynurenine, tryptophan, valine and isoleucine) were observed to be higher and three AAs (i.e., GABA, aminobutyric acid and asparaginic acid) were lower in 80 patients with first-episode SZ after various antipsychotics treatment. In addition, there were 1 out of 31 AAs altered after olanzapine treatment and there were only 2 out of 31 AAs altered after risperidone treatment. Furthermore, serum triglyceride (TG) was markedly upregulated after olanzapine treatment, while Apolipoprotein A1 (ApoA1) was generally upregulated after risperidone treatment in patients with first-episode SZ. Conclusions Taken together, antipsychotic treatment can affect the plasma levels of AAs in patients with first-episode SZ, and olanzapine and risperidone have differential effects on the levels of AAs. (AU)

Effect of pneumatic leg compression on phenylephrine dose for hypotension prophylaxis via variable rate infusion at cesarean delivery: an unblinded randomized controlled trial.

BACKGROUND: Phenylephrine infusion is recommended to prevent spinal hypotension during cesarean delivery (CD) but may be associated with dose-dependent side effects. We hypothesized that adding intermittent pneumatic compression (IPC) of the lower legs to a variable-rate phenylephrine infusion will reduce the dose of phenylephrine required during CD. METHODS: Seventy-six healthy women undergoing elective CD under combined spinal-epidural anesthesia were randomly assigned to IPC or control groups (n = 38 per group). After spinal anesthesia, IPC of the lower legs was initiated in the IPC group, and all women received a phenylephrine infusion starting at 25 µg·min-1 and increasing by 16.7 µg·min-1 for systolic blood pressure (SAP) < 90% baseline. If hypotension (SAP < 80% baseline) occurred, 100 µg phenylephrine bolus was administered. The primary outcome was the dose of phenylephrine per minute. RESULTS: The dose of phenylephrine per minute (34.4 ±â€¯7.3 µg·min-1 vs. 40.9 ±â€¯9.5 µg·min-1, P = 0.001; mean difference -6.6 µg·min-1, 95% CI -10.5 to -2.7 µg·min-1) and the incidence of hypotension (24% vs. 55%, P = 0.005) were lower in the IPC group than in the control group. There were no significant differences between the two groups in the total dose of phenylephrine (603.2 ±â€¯217.1 µg vs. 706.2 ±â€¯247.5 µg, P = 0.058; mean difference -102.9 µg, 95% CI -209.4 to 3.5 µg), maternal side effects, or neonatal outcomes. CONCLUSIONS: Intermittent pneumatic compression combined with a variable-rate phenylephrine infusion reduced the phenylephrine dose per minute and the incidence of hypotension during CD under spinal anesthesia.

[Bacterial community diversity in human Demodex mites].

OBJECTIVE: To investigate the bacterial community diversity in human Demodex mites, so as to provide insights into unraveling the role of human Demodex mites in them caused infectious diseases. METHODS: From June to July 2023, Demodex mites were collected from the faces of college students in a university in Wuhu City using the adhesive tape method, and the V4 region of 16S ribosomal RNA (16S rRNA) gene and the internal transcribed spacer (ITS) gene of nuclear ribosomal DNA were amplified on an Illumina PE250 high-throughput sequencing platform. Sequencing data were spliced according to the overlapping relations and filtered to yield effective sequences, and operational taxonomic units (OTUs) was clustered. The diversity index of obtained OUTs was analyzed, and the structure of the bacterial community was analyzed at various taxonomic levels. RESULTS: A total of 57 483 valid sequences were obtained using 16S rRNA gene sequencing, and 159 OUTs were classified according to similarity. Then, OUTs at a 97% similarity were included for taxonomic analyses, and the bacteria in Demodex mites belonged to 14 phyla, 20 classes, 51 orders, 72 families, and 94 genera. Proteobacteria was the dominant phylum, and Vibrio, Bradyrhizobium and Variovorax were dominant genera. A total of 56 362 valid sequences were obtained using ITS gene sequencing, and 147 OTUs were obtained, which belonged to 5 phyla, 17 classes, 34 orders, 68 families, and 93 genera and were annotated to Ascomycota, Basidiomycota and Chytridiomycota, with Ascomycota as the dominant phylum, and Alternaria alternata, Epicoccum, Penicillium, and Sarocladium as dominant genera. CONCLUSIONS: There is a high diversity in the composition of bacterial communities in human Demodex mites, with multiple types of microorganisms and high species abundance.

[Analysis of active components of Acorus tatarinowii extracts and its activity against dust mites].

OBJECTIVE: To investigate the activity of Acorus tatarinowii extracts against dust mites, and to isolate and characterize active ingredient of A. tatarinowii extracts. METHODS: The essential oil components were extracted from A. tatarinowii rhizome powder by rotary evaporation with methanol as solvents, followed by petroleum ether extraction and rotary evaporation. The essential oil was mixed with Tween-80 at a ratio of 1:1 and diluted into concentrations of 1.000 00%, 0.500 00%, 0.250 00%, 0.125 00%, 0.062 50% and 0.031 25%, while diluted Tween-80 served as controls. A. tatarinowii essential oil at each concentration (200 µL) was transferred evenly to filter papers containing 100 adult mites, with each test repeated in triplicate, and controls were assigned for each concentration. Following treatment at 25 °C and 75% relative humidity for 24 h, the mean corrected mortality of mites was calculated. The essential oil components were separated by silica gel column chromatography, and the essential oil was prepared in the positive column of medium pressure; and then, each component was collected. Silica gel column chromatography was run with the mobile phase that consisted of petroleum ether solution containing 10% ethyl acetate and pure ethyl acetate, detection wavelength of 254 nm, positive silica gel column as the chromatography column, and room temperature as the column temperature. Each component of the purified A. tatarinowii essential oil was diluted into 1.000 00% for acaricidal tests. The components with less than 100% acaricidal activity were discarded, and the remaining components were diluted into 50% of the previous-round tests for subsequent acaricidal tests. The components with acaricidal activity were subjected to high-performance liquid chromatography, liquid chromatography-mass spectrometry and pulsed-Fourier transform nuclear magnetic resonance spectroscopy. The structure of active monomer compounds was determined by standard spectral library retrieval and literature review. RESULTS: A. tatarinowii essential oil at concentrations of 1.000 00%, 0.500 00%, 0.250 00% and 0.125 00% killed all dust mites, and the corrected mortality was all 100%. Exposure to A. tatarinowii extracts at an effective concentration of 0.062 50% for 24 hours resulted in 94.33% mortality of dust mites. Six components (A to F) were separated using gel column chromatography, and components D and E both showed a 100% acaricidal activity against dust mites at a concentration of 0.50000%. In addition, Component D was identified as isoeugenol methyl ether, and Component E as ß-asarinol. CONCLUSIONS: The extract of A. tatarinowii essential oil has acaricidal activity, and the isoeugenol methyl ether shows a remarkable acaricidal activity against dust mites.

Dose-Painting Proton Radiotherapy Guided by Functional MRI in Non-enhancing High-Grade Gliomas.

AIMS: This study aimed to demonstrate the feasibility and evaluate the dosimetric effect and clinical impact of dose-painting proton radiotherapy (PRT) guided by functional MRI in non-enhancing high-grade gliomas (NE-HGGs). MATERIALS AND METHODS: The 3D-ASL and T2 FLAIR MR images of ten patients with NE-HGGs before radiotherapy were studied retrospectively. The hyperintensity on T2 FLAIR was used to generate the planning target volume (PTV), and the high-perfusion volume on 3D-ASL (PTV-ASL) was used to generate the simultaneous integrated boost (SIB) volume. Each patient received pencil beam scanning PRT and photon intensity-modulated radiotherapy (IMRT). There were five plans in each modality: (1) Uniform plans (IMRT60 vs. PRT60): 60Gy in 30 fractions to the PTV. (2)-(5) SIB plans (IMRT72, 84, 96, 108 vs. PRT72, 84, 96, 108): Uniform plan plus additional dose boost to PTV-ASL in 30 fractions to 72, 84, 96, 108 Gy. The dosimetric differences between various plans were compared. The clinical effects of target volume and organs at risk (OARs) were assessed using biological models for both tumor control probability (TCP) and normal tissue complication probability (NTCP). RESULTS: Compared with the IMRT plan, the D2 and D50 of the PRT plans with the same prescription dose increased by 1.27-4.12% and 0.64-2.01%, respectively; the R30 decreased by > 32%; the dose of brainstem and chiasma decreased by > 27% and >32%; and the dose of normal brain tissue (Br-PTV), optic nerves, eyeballs, lens, cochlea, spinal cord, and hippocampus decreased by > 50% (P < 0.05). The maximum necessary dose was 96GyE to achieve >98% TCP for PRT, and it was 84Gy to achieve >91% TCP for IMRT. The average NTCP of Br-PTV was 1.30% and 1.90% for PRT and IMRT at the maximum dose escalation, respectively. The NTCP values of the remaining OARs approached zero in all PRT plans. CONCLUSION: The functional MRI-guided dose escalation using PRT is feasible while sparing the OARs constraints and demonstrates a potential clinical benefit by improving TCP with no or minimal increase in NCTP for tissues outside the PTV. This retrospective study suggested that the use of PRT-based SIB guided by functional MRI may represent a strategy to provide benefits for patients with NE-HGGs.

The injury progression in acute blast-induced mTBI in rats reflected by DTI and immunohistochemical examination.

Diffusion tensor imaging (DTI) has emerged as a promising neuroimaging tool for detecting blast-induced mild traumatic brain injury (bmTBI). However, lack of refined acute-phase monitoring and reliable imaging biomarkers hindered its clinical application in early diagnosis of bmTBI, leading to potential long-term disability of patients. Here, we used DTI in a rat model of bmTBI generated by exposing to single lateral blast waves (151.16 and 349.75 kPa, lasting 47.48 ms) released in a confined bioshock tube (BST-I) to investigate whole-brain DTI changes in the acute-phase of bmTBI at 1, 3, 7 days after injury. Combined assessment of immunohistochemical analysis, transmission electron microscopy (TEM) and behavioral readouts allowed for linking DTI changes to synchronous cellular damages and identifying stable imaging biomarkers. The corpus callosum (CC) and brainstem were identified as predominantly affected regions, in which reduced fractional anisotropy (FA) was detected as early as the first day after injury, with a maximum decline occurring at 3 days after injury before returning to near normal levels by 7 days. Axial diffusivity (AD) values within the CC and brainstem also significantly reduced at 3 days after injury. In contrast, the radial diffusivity (RD) in the CC showed acute elevation, peaking at 3 days after injury before normalizing by the 7-day time point. Damages to nerve fibers, including demyelination and axonal degeneration, progressed in lines with changes in DTI parameters, supporting a real-time macroscopic reflection of microscopic neuronal fiber injury by DTI. The most sensitive biomarker was identified as a decrease in FA, AD and an increase in RD within the CC on the third day after injury, supporting the diagnostic utility of DTI in cases of bmTBI in the acute phase.

[Current status of tuberculosis burden in China].

Tuberculosis, caused by Mycobacterium tuberculosis, is an infectious disease that most often affects the lungs. China is still among the high-burden tuberculosis countries in the world. Although the estimated incidence of tuberculosis in China has declined in recent years, the declining rate is slow. It still faces major issues such as a slower rate of decline, a widening gap between estimated and notified incidence, higher risk among middle-aged and older adults, a high number of cases among agriculture and related workers, and a heavier disease burden in the country's western regions. In addition, latent tuberculosis infection, drug-resistant tuberculosis, tuberculosis coinfection with HIV, and extrapulmonary tuberculosis have also exacerbated the disease burden of tuberculosis to some extent. This paper reviewed the epidemic characteristics of tuberculosis, the epidemiological triad, three links and two factors in the transmission process, the disease burden, and other aspects to provide a reference for formulating prevention and control strategies on tuberculosis.

[Analysis of highly cited papers in Chinese Journal of Epidemiology from 2020 to 2023].

Objective: To analyze the characteristics of highly-cited papers in Chinese Journal of Epidemiology from 2020 to 2023, and provide a basis for subsequent paper solicitation and identify research hotspots. Methods: On December 9, 2023, the citation frequency of each paper in Chinese Journal of Epidemiology from 2020 to 2023 was obtained from China National Knowledge Infrastructure. The total citation frequency of each paper was sorted using Excel 2016 software, and papers with citation frequency ≥30 were extracted for analysis. The keywords of the papers and Contents in Brief were analyzed. Results: A total of 1 317 papers were included in the analysis, of which 389, 342, 308 and 278 papers were included from 2020 to 2023. The total citation frequency was 11 873, and all papers were cited with an average citation frequency of 9. The keywords with high citation frequency in the papers included 2019-nCoV, hypertension, colorectal tumor, hand-foot-mouth disease, hepatitis B. and the average frequency of citation were 162, 77, 62, 51 and 47, respectively. There were 15 highly cited Contents in Brief in total, 11 of which are vital Contents in Brief or unique Contents in Brief, including Response to COVID-19 Epidemic, China Kadoorie Biobank, Epidemiological Research on Infectious Diseases, Healthy Ageing, Colorectal Cancer Prevention and Control, Prevention and Control of Hepatitis B, Quality Assessment of Cancer Screening Guidelines and Consensus, The 40th Anniversary of Chinese Journal of Epidemiology, Expert Forum, Review, Standard-Protocol-Guide. The total citation frequency was 3 951, accounting for 72.6% (3 951/5 438) of highly cited papers. Conclusions: In the past four years, the highly cited papers of this journal mainly focused on the research field of emerging infectious diseases and chronic diseases. The response to the 2019-nCoV epidemic highlights the academic leading role. The effect of selecting and planning a topic, commissioning authors to write on given topics and making an arrangement in advance with a subject for contribution to vital Contents in Brief or unique Contents in Brief of this journal is pronounced, and the academic influence of the journal continues to improve.