Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

Prediction by uterine artery Doppler screening of small-for-gestational-age neonates at 19-24 weeks' gestation.

OBJECTIVE: Small-for-gestational-age (SGA) neonates are at increased risk of perinatal mortality and morbidity. We aimed to investigate the performance of uterine artery pulsatility index (UtA-PI) at 19-24 weeks' gestation to predict the delivery of a SGA neonate in a Chinese population. METHODS: This was a retrospective cohort study using data obtained between January 2010 and June 2018. Doppler ultrasonography was performed at 19-24 weeks' gestation. SGA was defined as birth weight below the 10th centile according to the INTERGROWTH-21st fetal growth standards. The performance of UtA-PI to predict the delivery of a SGA neonate was assessed using receiver-operating-characteristics (ROC)-curve analysis. RESULTS: We included 6964 singleton pregnancies, of which 748 (11%) delivered a SGA neonate, including 115 (15%) women with preterm delivery. Increased UtA-PI was associated with an elevated risk of SGA, both in neonates delivered at or after 37 weeks' gestation (term SGA) and those delivered before 37 weeks (preterm SGA). The areas under the ROC curve (AUCs) for UtA-PI were 64.4% (95% CI, 61.5-67.3%) and 75.8% (95% CI, 69.3-82.3%) for term and preterm SGA, respectively. The performance of combined screening by maternal demographic/clinical characteristics and estimated fetal weight in the detection of term and preterm SGA was improved significantly by the addition of UtA-PI, although the increase in AUC was modest (2.4% for term SGA and 4.9% for preterm SGA). CONCLUSIONS: This is the first Chinese study to evaluate the role of UtA-PI at 19-24 weeks' gestation in the prediction of the delivery of a neonate with SGA. The addition of UtA-PI to traditional risk factors improved the screening performance for SGA, and this improvement was greater in predicting preterm SGA compared with term SGA. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

[Clinical characteristics of programmed cell death-1 inhibitor-associated hypophysitis].

Objective: To explore the clinical features of programmed cell death-1 (PD-1) inhibitor-associated hypophysitis and improve the understanding of the disease. Methods: For the present retrospective case series study, the clinical data of patients with PD-1 inhibitor-associated hypophysitis who were treated at the Affiliated Hospital of Hebei University and the 3rd Hospital of Hebei Medical University from January 2020 to May 2023 were collected for analysis of clinical manifestations and prognosis. Results: Fifteen cases of PD-1 inhibitor-induced hypophysitis were included, with 13 males and 2 females. The mean age of onset was (62.1±7.5) years, and the median time of onset was 6.5 (4.7, 11.6) cycles of PD-1 inhibitor. At diagnosis, 14 patients complained of gastrointestinal symptoms, and 12 patients complained of fatigue. There were 12, 1, 1, 5, and 1 cases of hyponatremia, hypokalemia, hypoglycemia, hypotension, and fever, respectively. Secondary adrenocortical insufficiency occurred in all cases. Moreover, four patients had secondary hypothyroidism, and two patients had secondary hypogonadism. Posterior pituitary hypofunction was not found. Pituitary MRI showed one case each of vacuolar sella turcica, pituitary cystic lesion, pituitary stalk slightly shifted to the left, high metabolism in the sella turcica, and pituitary abnormal signal, while no abnormalities were found in 11 cases. The follow-up time was (47.66±11.93) weeks. At the last follow-up, one patient's serum levels of adrenocorticotropic hormone and cortisol returned to normal. Conclusions: Hypophysitis associated with PD-1 inhibitors occurs later, and gastrointestinal symptoms and fatigue are the most common clinical manifestations. PD-1 inhibitor-associated hypophysitis mainly manifests as adrenocortical hypofunction, and some cases manifest as hypothyroidism and hypogonadism. In addition, patients with PD-1 inhibitor-associated hypophysitis show no obvious imaging changes in the pituitary gland.

[Study on transcriptome characteristics of respiratory syncytial virus bronchiolitis in children by RNA sequencing].

To explore the biological characteristics related to the pathogenesis and severity of respiratory syncytial virus (RSV) bronchiolitis by RNA sequencing of white blood cells in children with RSV bronchiolitis. This study is a case-control study. A total of 87 children diagnosed with bronchiolitis and RSV antigen positive and/or RSV nucleic acid positive in the pediatric respiratory department of the Second Affiliated Hospital of Wenzhou Medical University from October 2019 to April 2022 were selected as the case group. The case group was divided into three groups based on the condition: mild, moderate, and severe, and there were two groups according to the presence or absence of atopic symptoms: the atopic group and the non-atopic group, forty healthy children in the same period were selected as the control group. The whole blood leukocyte RNA of the children in the case group and the control group was extracted for RNA sequencing, and the data were analyzed to obtain differentially expressed genes (DEGs). Then, the immunobiological pathways and genes related to the pathogenesis, disease condition, and atopy were screened through Gene Ontology (GO) annotation, Kyoto Gene and Genome Encyclopedia (KEGG) annotation, and protein interaction network (PPI) construction methods. Construct the weighted gene co-expression network analysis (WGCNA) module to identify potential biological indicators related to disease severity.Compared with the control group, the case group had a total of 1 782 DEGs, including 1 586 upregulated genes and 196 downregulated genes. The GO pathway enrichment of DEGs is mainly enriched in molecular functions such as peroxidase activity and oxidoreductase activity. In the cytological components, it is mainly enriched in cytoplasmic vesicle lumen and secretory granule lumen. In biological processes, it is mainly enriched in processes such as neutrophil activation involved in immune responses, neutrophil degranulation, and neutrophil activation. KEGG analysis is mainly concentrated in the signal pathway of the viral protein interaction with cytokine and cytokine receptor. A PPI network was constructed to screen four genes at the core position, including CCL2, IL-10, MMP9 and JUN. The DEGs obtained by comparing different disease groups with the control group are mainly enriched in retrograde endocannabinoid signaling and cell apoptosis pathways. WGCNA analysis showed that the brown module related to oxygen saturation was most closely related to the disease, and its gene was mainly enriched in the RNA helicase retinoic acid inducible gene-I (RIG-I) like receptor signal pathway. There are 230 specific DEGs in the atopic group and 444 in the non-atopic group. KEGG enrichment analysis results show that both groups are enriched to NF-κB signaling pathway, the characteristic does not cause significant changes in immune response and transcriptome characteristics in children with RSV bronchiolitis. In conclusion, neutrophil activation, degranulation pathway and signal pathway of interaction between viral protein and cytokine and cytokine receptor are involved in the immune response of RSV bronchiolitis host. CCL2, IL-10, MMP9 and JUN genes may be associated with the pathogenesis. They might be potential biomarkers related to disease severity in RIG-I like receptors, cell apoptosis, and endogenous cannabinoid related signaling pathways.

[The ninth edition of TNM staging for lung cancer: precise staging for precise diagnosis and treatment].

The ninth edition of TNM staging for lung cancer has been announced at the 2023 World Lung Cancer Congress and implemented from January 1, 2024. The focus of the ninth TNM staging change is dividing N2 into N2a and N2b, as well as M1c into M1c1 and M1c2. Although the T staging has not changed, it has played an important role in verifying the eighth edition of the T staging. The subdivision of stage N2 has led some patients with ⅢA of the eighth edition to experience ascending or descending stages, which will more accurately help to assess the condition and prognosis of patients with mediastinal lymph node metastasis, as well as the design of related clinical studies. Modifying the M1c staging will help define oligometastasis and explore new treatment models in the future. The ninth edition of the TNM staging system provides a more detailed division of different tumor loads, but there is no clear explanation for the staging of lung cancer after neoadjuvant therapy. Further data analysis is needed, and it is expected to be answered in the tenth edition of TNM staging.

[Microglia differential genes and their functions in paraquat-induced Parkinson's disease-like in mice's brains based on single-cell RNA sequencing].

Objective: To analyze the differential genes and related signaling pathways of microglia subpopulations in Parkinson's disease (PD) -like mouse brains induced by paraquat (PQ) based on single-cell RNA sequencing, and provide clues to elucidate the mechanism of PQ-induced PD-like changes in the brain of animals. Methods: In September 2021, six male 6-week-old C57BL/6 mice were randomly divided into control group and experimental group (three mice in each group) . The mice were injected with saline, 10.0 mg/kg PQ intraperitoneally, once every three days, and 10 consecutive injections were used for modeling. After infection, the brains of mice were taken and 10×Genomics single-cell RNA sequencing was performed. Microglia subpopulations were screened based on gene expression characteristics, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The differential genes of microglia subpopulations between the experimental group and control group were further screened, and functional enrichment analysis was performed using bioinformatics tools. Mouse microglia (BV2 cells) were treated with 0, 60, 90 µmol/L PQ solution, respectively. And real-time fluorescence quantitative PCR experiments were conducted to validate the expressions of differential genes hexokinase 2 (Hk2) , ATPase H+ Transporting V0 Subunit B (Atp6v0b) and Neuregulin 1 (Nrg1) . Results: Cluster 7 and Cluster 20 were identified as microglia subpopulations based on the signature genes inositol polyphosphate-5-phosphatase d, Inpp5d (Inpp5d) and transforming growth factor beta receptor 1 (Tgfbr1) , and they reflected the microglia-activated M2 phenotype. The bioinformatics analysis showed that the characteristic genes of identified microglia subpopulations were enriched in endocytosis. In terms of molecular function, it mainly enriched in transmembrane receptor protein kinase activity and cytokine binding. The up-regulated genes of Cluster 7 were mainly enriched in lysosomal pathway, endocytosis pathway, and down-regulated genes were mainly enriched in neurodegenerative disease and other signaling pathways. The up-regulated genes of Cluster 20 were mainly enriched in signaling pathways related to PD, and down-regulated genes were mainly enriched in cyclic adenosine 3', 5'-monophosphate (cAMP) signaling pathways, neurological development, synaptic function and other signaling pathways. The results of real-time fluorescence quantitative PCR showed that the expressions of Hk2 mRNA and Atp6v0b mRNA increased and the expression of Nrg1 mRNA decreased in the 90 µmol/L PQ-treated BV2 cells compared with the 0 µmol/L, and the differences were statistically significant (P<0.05) . Conclusion: Microglia are activated in the PQ-induced PD-like mouse model and polarized toward the M2 phenotype. And their functions are associated with lysosomal (endocytosis) , synaptic functions and the regulation of PD-related pathways.

[Clinical characteristics of sudden sensorineural hearing loss with acute cerebral infarction].

Objective: To analyze the clinical and imaging features of patients with sudden sensorineural deafness and acute cerebral infarction in order to provide evidence for early recognition of such diseases. Methods: This was a case series reporting study. A retrospective analysis was performed on the clinical and imaging data of 29 patients with sudden hearing loss (SHL) who admitted to the Otolaryngology Head and Neck Surgery Department of Beijing Tiantan Hospital from January 2017 to December 2021 and diagnosed with acute cerebral infarction using MRI-DWI. Results: The patients were aged 31-71 years, with an average age of 56±12 years, and 82.8% (24/29) were men. In total, 82.8% (24/29) of the patients had three or more atherosclerotic risk factors, and 24.1% (7/29) had a history of SHL. The hearing types were flat and total deafness: 86.2% (25/29) of the patients had severe hearing loss, 27.6% (8/29) had bilateral SHL, 17.2% (5/29) had further hearing loss during hospitalization, and 82.8% (24/29) had dizziness or vertigo at the onset. The signs of central nervous system involvement mainly included speech impairment, diplopia, dysphagia, central facial paralysis, facial and limb hypoesthesia, ataxia, and decreased muscle strength. Imaging evaluation showed that 21 cases were located in the posterior circulation supply area and 8 cases in the anterior circulation supply area. Additionally, 82.8% (24/29) patients had vertebrobasilar artery stenosis, and 58.6% (17/29) patients had severe vertebrobasilar artery stenosis or occlusion. Conclusions: Patients with SHL who progress to cerebral infarction often have multiple atherosclerotic risk factors and SHL. Most of the patients are middle-aged and older men who often complain of dizziness or dizziness accompanied by severe flat and total deafness with unilateral or bilateral SHL. Imaging findings suggest that most patients have posterior circulation infarction, often accompanied by severe stenosis or occlusion of the vertebrobasilar artery.

[Clinical analysis of 244 cases with abdominal wall endometriosis].

Objective: To investigate the clinical characteristics, diagnosis, treatment, outcomes and prognostic factors of abdominal wall endometriosis (AWE). Methods: A total of 265 AWE patients who underwent surgical treatment in The First Affiliated Hospital of Anhui Medical University from January 2010 to April 2023 were retrospectively selected, and 244 patients had complete follow-up data. According to different depth of lesions, the enrolled patients were divided into three types: type Ⅰ (subcutaneous fat layer, n=30), type Ⅱ (anterior sheath muscle layer, n=174) and type Ⅲ (peritoneum layer, n=40). The general clinical features, perioperative conditions, recurrent outcome and prognostic factors were analyzed in three types. Results: (1) Compared with type Ⅲ patients, the age of onset, parity and incidence of pelvic endometriosis were significantly decreased in type Ⅱ patients [(32.0±4.0) vs (30.0±4.6) years, 1.6±0.6 vs 1.4±0.5, 10.0% (4/40) vs 1.7% (3/174), respectively; all P<0.05], while the proportion of patients with transverse incision was significantly increased [37.5% (15/40) vs 67.3% (115/171); P<0.01]. The first symptoms of type Ⅰ and type Ⅱ were mainly palpable mass in the abdominal wall [73.3% (22/30), 63.2% (110/174), respectively], but the first symptom of type Ⅲ was pain in the abdominal wall [55.0% (22/40); all P<0.05]. (2) No matter the results of preoperative B-ultrasound or intraoperative exploration, the lesion diameters of type Ⅰ, type Ⅱ and type Ⅲ showed significant upward trends (all P<0.05). The proportions of lesion diameter≥3 cm in type Ⅱ and type Ⅲ [67.8% (118/174), 80.0% (32/40)] were significantly higher than that in type Ⅰ (all P<0.05). The median operation time and blood loss of type Ⅰ and Ⅱ were significantly lower than those of type Ⅲ (type Ⅰ vs type Ⅲ: 37.5 vs 50.0 minutes, 10 vs 20 ml, all P<0.05; type Ⅱ vs type Ⅲ: 35.0 vs 50.0 minutes, 10 vs 20 ml, all P<0.05). (3) The median follow-up time was 49 months, the overall symptom remission rate was 98.4% (240/244), and the recurrence rate was 7.0% (17/244). There were no significant differences in recurrence rate and recurrence free time among three types (all P>0.05). Multivariate regression analysis showed that the depth, number, diameter of lesions and postoperative adjuvant medication were not significant factors for postoperative recurrence (all P>0.05). Conclusions: The clinical manifestations of type Ⅲ are the most serious, including obvious abdominal pain symptoms, larger lesion diameter, prolonged operation time, increased intraoperative blood loss and increased incidence of pelvic endometriosis. Complete resection of lesions is an effective treatment for AWE, with high symptom remission rate and low recurrence rate. The depth, number, diameter of lesions and postoperative adjuvant medication are not risk factors for recurrence.

[Regulating the immune response to carbon tetrachloride-induced liver fibrosis in mice by blocking inducible co-stimulatory molecules and interleukin-33].

Objective: To investigate the effects of combined blockade of interleukin-33 (IL-33) and inducible co-stimulatory molecule (ICOS) on carbon tetrachloride-induced chronic liver fibrosis and imbalance of T helper lymphocyte subsets in mice. Methods: There were 40 BALB/c mice in each model and control group. Flow cytometry was used to determine the proportion of Th1/Th2/Th17 cells in the splenic lymphocyte suspension of mice, the expression levels of interferon γ, IL-4, and IL-17 in the splenic lymphocyte suspension of liver fibrosis mice after combined blockade of IL-33 and ICOS, and the pathological changes of liver histopathology in mice with liver fibrosis. Two independent sample t-test was used to compare data between groups. Results: Compared with the non-blocking group, the proportion of Th2 and Th17 cells in the IL-33/ICOS blocking group was significantly down-regulated (Th2: 65.96% ± 6.04% vs. 49.09% ± 7.03%; Th17: 19.17% ± 4.03% vs. 9.56% ± 2.03%), while the proportion of Th1 cells and Th1/Th2 ratio were up-regulated (Th1: 17.14% ± 3.02% vs. 31.93% ± 5.02%; Th1/Th2: 0.28 ± 0.06 vs. 0.62 ± 0.23), and the difference was statistically significant (t = 5.15, 6.03, 7.14, 4.28, respectively, with P < 0.05). After entering the chronic inflammation stage of liver fibrosis in mice (10 weeks), compared with the non-blocking group, the expression levels of IL-4 and IL-17 in the blockade group were significantly down-regulated [IL-4: (84.75 ± 14.35) pg/ ml vs. (77.88 ± 19.61) pg/ml; IL-17: (72.38 ± 15.13) pg/ml vs. (36.38 ± 8.65) pg/ml], while the expression of interferon γ was up-regulated [(37.25 ± 11.51) pg/ml vs. (77.88 ± 19.61) pg/ml], and the difference was statistically significant (t: IL-4: 4.71; IL-17: 5.84; interferon γ: 5.05, respectively, with P < 0.05). Liver histopathological results showed that hepatic necrosis, hepatic lobular structural disorder, and fibrous tissue hyperplasia were significantly lower in the blockade group than those in the non-blocking group at 13 weeks of liver fibrosis. Conclusion: Combined blockade of the ICOS signaling pathway and IL-33 can regulate Th2 and Th17 polarization, down-regulate the inflammatory response, and inhibit or prevent the occurrence and progression of fibrosis.

[A multicenter study to test the reliability and validity of the frailty assessment scale for elderly patients with inguinal hernia and to evaluate the value of clinical application].

Objectives: To verify the reliability and validity of the frailty assessment scale for elderly patients with inguinal hernia and to evaluate the value of its clinical application. Methods: A convenience sampling method was used to collect 129 geriatric patients who underwent inguinal hernia surgery from January 2018 to January 2023 in nine hospitals in Liaoning Province. There were 120 males and 9 females, of whom 89 patients were 60 to <75 years old, 33 patients were 75 to <85 years old and 7 patients were ≥85 years old. The 129 patients included 11 elderly patients with inguinal hernia who had recovered from preoperative infection with COVID-19. Statistical methods such as Cronbach's coefficient, Kaiser-Meyer-Olkin test, Bartlett's test, Pearson's correlation analysis, etc. were calculated to verify the reliability indexes such as feasibility, content validity, structural validity, criterion-related validity, internal consistency reliability, and re-test reliability. Taking the 5-item modified frailty index (5-mFI) as the gold standard, the area under the curve was used to analyze the ability of the two scales to predict the occurrence of postoperative acute urinary retention, postoperative delirium, poor incision healing, operative hematoma seroma, and postoperative complications. Results: The frailty assessment scale for elderly patients with inguinal hernia showed good reliability and validity (valid completion rate of 99.2%; item content validity index of 1.000, and the scale content validity index of 1.000; exploratory factor analysis extracted a total of 1 principal component, and factor loadings of each item of 0.565 to 0.873; the AUC for frailty diagnosis using 5-mFI as the gold standard of 0.795 (P<0.01) Cronbach's coefficient of 0.916, retest reliability coefficient of 0.926), it could effectively predict postoperative acute urinary retention, delirium, hematoma seroma in the operative area and total complications (AUC of 0.746, 0.870, 0.806, and 0.738, respectively; all P<0.05), and prediction efficiency was higher than that of 5-mFI (AUC of 0.694, 0.838, 0.626 and 0.641, P<0.05 for delirium only), but both scales were inaccurate in predicting poor incision healing (AUC of 0.519, P=0.913 for the frailty assessment scale and 0.455, P=0.791 for the 5-mFI). Conclusions: The frailty assessment scale for elderly patients with inguinal hernia is reliable and significantly predicts the occurrence of postoperative adverse events in elderly inguinal hernia patients. The scale can also be used for preoperative frailty assessment in elderly patients with inguinal hernia after rehabilitation from COVID-19 infection.

[Analysis of the prevalence of dyslipidemia and correlative factors in Tajik population in Pamir Plateau of Xinjiang].

Objective: To investigate the prevalence of dyslipidemia and the level of blood lipids among Tajik people in Pamir Plateau, Xinjiang, and explore the related factors of dyslipidemia. Methods: It is a retrospective cross-sectional study. A multi-stage cluster random sampling survey was conducted among 5 635 Tajiks over 18 years old in Tashkorgan Tajik Autonomous County, Xinjiang Province from May to October 2021. Data were collected through questionnaire survey (general information, medical history, and personal history), physical examination (height, weight, waist, and blood pressure) and blood test (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density cholesterol (HDL-C)) to analyze the dyslipidemia and its risk factors among Tajiks. Results: The age of Tajik participants was (41.9±15.0) years, including 2 726 males (48.4%). The prevalence of borderline high TC, high LDL-C and high TG levels were 17.2%, 14.7% and 8.9%, respectively. The prevalence of high TC, high LDL-C, high TG and low HDL-C were 4.1%, 4.9%, 9.4% and 32.4%, respectively, and the prevalence of dyslipidemia was 37.0%. There is a positive correlation between male,higher education level, higher body mass index (BMI) value,waist circumference, living in town, smoking and dyslipidemia. Conclusions: The low prevalence of high TC, high LDL-C, high TG and high prevalence of low HDL-C was a major characteristic of Tajik people in Pamir Plateau of Xinjiang. The lower rates of overweight and obesity may be one of the reasons for the lower prevalence of dyslipidemia among Tajik.

High species diversity in Diaporthe associated with citrus diseases in China.

Species in Diaporthe have broad host ranges and cosmopolitan geographic distributions, occurring as endophytes, saprobes and plant pathogens. Previous studies have indicated that many Diaporthe species are associated with Citrus. To further determine the diversity of Diaporthe species associated with citrus diseases in China, we conducted extensive surveys in major citrus-producing areas from 2017-2020. Diseased tissues were collected from leaves, fruits, twigs, branches and trunks showing a range of symptoms including melanose, dieback, gummosis, wood decay and canker. Based on phylogenetic comparisons of DNA sequences of the internal transcribed spacer regions (ITS), calmodulin (cal), histone H3 (his3), translation elongation factor 1-alpha (tef1) and beta-tubulin (tub2), 393 isolates from 10 provinces were identified as belonging to 36 species of Diaporthe, including 32 known species, namely D. apiculata, D. biconispora, D. biguttulata, D. caryae, D. citri, D. citriasiana, D. compacta, D. discoidispora, D. endophytica, D. eres, D. fusicola, D. fulvicolor, D. guangxiensis, D. hongkongensis, D. hubeiensis, D. limonicola, D. litchii, D. novem, D. passifloricola, D. penetriteum, D. pescicola, D. pometiae, D. sackstonii, D. sennicola, D. sojae, D. spinosa, D. subclavata, D. tectonae, D. tibetensis, D. unshiuensis, D. velutina and D. xishuangbanica, and four new species, namely D. gammata, D. jishouensis, D. ruiliensis and D. sexualispora. Among the 32 known species, 14 are reported for the first time on Citrus, and two are newly reported from China. Among the 36 species, D. citri was the dominant species as exemplified by its high frequency of isolation and virulence. Pathogenicity tests indicated that most Diaporthe species obtained in this study were weakly aggressive or non-pathogenic to the tested citrus varieties. Only D. citri produced the longest lesion lengths on citrus shoots and induced melanose on citrus leaves. These results further demonstrated that a rich diversity of Diaporthe species occupy Citrus, but only a few species are harmful and D. citri is the main pathogen for Citrus in China. The present study provides a basis from which targeted monitoring, prevention and control measures can be developed. Citation: Xiao XE, Liu YD, Zheng F, et al. 2023. High species diversity in Diaporthe associated with citrus diseases in China. Persoonia 51: 229-256. doi: 10.3767/persoonia.2023.51.06.

Protective effects of recombinant lactoferrin with different iron saturations on enteritis injury in young mice.

Infant intestinal development is immature and, thus, is vulnerable to bacterial and viral infections, which damage intestinal development and even induce acute enteritis. Numerous studies have investigated that lactoferrin (LF) has protective effects on the intestine and may play a role in preventing intestinal inflammation in infants. Lactoferrin is divided into 2 types, namely apo-LF and holo-LF, depending on the degree of iron saturation, which may affect its bioactivities. However, the role of LF iron saturation in protecting infant intestinal inflammation has not been clearly clarified. Therefore, in this study, young mice models with intestinal damage induced by lipopolysaccharides (LPS) in vivo and primary intestinal epithelial cells in vitro were constructed to enteritis injury in infants for investigation. The apo-LF and holo-LF were subsequently applied to the mouse models to investigate and compare their levels of protection in the intestinal inflammatory injury, as well as to identify which LF was most active. Moreover, the specific mechanism of the LF with optimal iron saturation was further investigated through Western blot assay. Results demonstrated that disease activity index, shortened length of colon tissue, and histopathological score were significantly decreased in the apo-LF group compared with those of the LPS group and the holo-LF group. In the apo-LF group, the concentration of LPS in the intestinal tract and the number of gram-negative bacteria colonies decreased significantly and the expression levels of proinflammatory factors in the colon tissue were downregulated, in comparison with those in the LPS group. The findings of this study thus verify that apo-LF can significantly alleviate enteritis injury caused by LPS, through regulating the PPAR-γ/PFKFB3/NF-κB inflammatory pathway.

[Effects of statins on mortality and neurologic outcomes in patients with traumatic brain injury: a meta-analysis].

Objective: To systematically evaluate the effects of statins on the mortality and neurologic function prognosis in patients with traumatic brain injury (TBI). Methods: The PubMed, Embase, the Cochrane Library, the Cochrane Clinical Controlled Trial Center Registry Database, Chinese Journal Full-text Database (CNKI), and WanFang database up to 2021.1 were searched to obtain clinical randomized controlled trials (RCTs) and retrospective cohort studies of statins in the treatment of TBI. Inclusion and exclusion criteria were used to screen literature and extract data. Ottawa scale and the RCT bias risk assessment tool was used for quality evaluation. Comprehensive Meta Analysis V3 statistical software for meta-analysis was applied. Results: Thirteen studies were included, with a total of 116, 500 patients, including 46, 933 patients using statins in the intervention group and 69, 567 patients in the control group. Meta-analysis results showed that compared with the control group, statins can reduce the mortality of TBI patients (OR=0.82, 95%CI: 0.74-0.92, P<0.01), significantly improve the neurologic outcomes of TBI patients (OR=0.19, 95%CI: 0.13-0.26, P<0.01), and reduce the levels of TNF-α and IL-1ß after TBI (TNF-α: OR=0.16, 95%CI: 0.07-0.34, P<0.01; IL-1ß: OR=0.08, 95%CI: 0.04-0.18, P<0.01), with statistically significant differences. Conclusion: Statins can reduce the mortality of patients with TBI and improve the neurologic outcomes. Their reduction of inflammation in the body may be the basis of potential treatment, but more high-quality RCTs are still warranted.

[Gender differences of genetic etiology in the incidence of major depressive disorder among Han freshmen].

Objective: To analyze the gender differences of genetic etiology in the incidence of major depression disorder among Han freshmen. Methods: A 1-year follow-up survey was carried out among 8 079 Han freshmen from Jining, Rizhao and Weifang without lifetime major depressive disorder (MDD) at baseline (April to October 2018) and 4 828 venous blood samples were also collected. After extracting DNA, Sequenom Mass Array time-of-flight mass spectrometry biochip technology was used to detect the genotypes of 17 single nucleotide polymorphisms (SNPs) MDD-related loci. Logistic regression was used for univariate analysis. Generalized multifactor dimension reduction was used to analyze gene-gene interactions. Composite International Diagnostic Interview (CIDI) 3.0 was used for MDD diagnosis. Results: The 1-year incidence of MDD among Han freshmen was 2.23% (95%CI: 1.91%-2.60%) and the gender difference of incidence between males (1.97%, 95%CI: 1.52%-2.56%) and females (2.39%, 95%CI: 1.98%-2.90%) was not statistically significant (P>0.05). AG genotype of rs768705 (nearby gene: TMEM161B) was a risk factor for MDD (OR=1.98, 95%CI: 1.24-2.83). The TC genotype of rs17727765 (nearby gene: CRYBA1) was only a risk factor for MDD in males (OR=9.61, 95%CI: 2.04-45.30). An 8-loci interaction model (PMFBP1, OLFM4, LHPP, ENOX1, TMEM161B, SPPL3, FBXL4 and L3MBTL2) could predict MDD in women with an accuracy rate of 60.05%. No effective prediction model was found for MDD in men. Conclusions: There might be gender differences in the genetic etiology of MDD. Further researches on the genetic causes of MDD in men should be explored.

[A meta-analysis on prevalence of primary angle-closure glaucoma in the middle-aged and elderly chinese population].

Objective: To evaluate the prevalence and relevant factors of primary angle-closure glaucoma (PACG) in the middle-aged and elderly (40 years old and above) Chinese population. Methods: Epidemiological literature (of English and/or Chinese language) on prevalence of PACG in China between 2000 and 2022 were retrieved from PubMed, Embase, Web of Science, CNKI, and Wanfang database. Two researchers conducted the process of document retrieval, inclusion, quality assessment and data extraction independently based on inclusion and exclusion criteria. Disagreement was resolved by consensus with a third researcher. The heterogeneity among studies was assessed by using the I2 statistics, and a corresponding model was used for the meta-analysis. Subgroup analysis (gender, age, survey date, place of residence, diagnostic criteria, and temperature zone), as well as sensitivity analysis and publication bias analysis, were conducted. Results: Twenty-three studies were included in this research. Among them, eight were of high-quality and fifteen were of middle-quality. In the past 20 years, the PACG prevalence in middle-aged and elderly (40 years and older) Chinese population was 1.35% (95%CI:1.08% to 1.61%). Chinese women (1.40%) were more likely to have PACG than men (0.96%, P<0.01). The PACG prevalence had a positive correlation with age (P<0.01). The prevalence was similar between urban (1.3%) and rural (1.2%, P=0.61) areas. The PACG prevalence from studies in which the diagnostic criteria of PACG requested the symptom of vision or optic nerve damage (1.1%) was lower than that those without such requirement (1.7%, P<0.01). In mid-temperate zone, the prevalence was higher (1.7%, P=0.02). Conclusions: The PACG prevalence in middle-aged and elderly (40 years old and above) Chinese population was 1.35% in the last 20 years. The prevalence of PACG varies across age, regions, and other variations. This risk is higher in the elderly, women, and people in cold regions among Chinese population.

[A randomized controlled trial of indobufen versus aspirin in the prevention of bridging restenosis after coronary artery bypass grafting].

Objective: To compare the efficacy and safety between indobufen and aspirin in the prevention of restenosis of bridge vessels at 1 year after off-pump coronary artery bypass grafting. Methods: This study was a prospective cohort study. We selected 152 patients who received coronary artery bypass grafting in Beijing Anzhen Hospital from December 2016 to December 2018. Patients were divided into the indobufen group and the aspirin group. Patients in the aspirin group were treated with aspirin and clopidogrel, and patients in the indobufen group were treated with indobufen and clopidogrel. During the 1-year follow-up, the rate of restenosis of saphenous vein bridge and internal mammary artery bridge, the rate of adverse cardiac events and adverse reactions were compared between the two groups. The levels of fibrinogen (FIB), D-dimer (D-D), thrombomodulin (TM) and thrombin-activatable fibrinolysis inhibitor (TAFI) were compared before and after antiplatelet therapy. Results: There were 76 cases in the indobufen group, including 57 males (75.0%), aged (60.3±6.6) years. There were 76 cases in the aspirin group, including 62 males (81.6%), aged (59.7±7.2) years. Baseline data were comparable between the two groups (P>0.05). During the follow-up, 3 cases were lost to follow up. Follow-up was completed in 74 patients in the indobufen group and 75 in the aspirin group. A total of 268 bridging vessels were grafted in the indobufen group and 272 in the aspirin group. One year after surgery, the patency rates of great saphenous vein bridge and internal mammary artery bridge were 94.5% (189/200) and 97.1% (66/68) in the indobuphen group, and 91.3% (189/207) and 96.9% (63/65) in the aspirin group, respectively. There was no significant difference in patency rate of great saphenous vein bridge and internal mammary artery bridge between the two groups (χ²=0.282, 0.345, P>0.05). The total incidence of adverse cardiac events was 5.4% (4/74) in the indobufen group and 6.7% (5/75) in the aspirin group (χ²=0.126, P>0.05). The overall incidence of gastrointestinal adverse reactions was significantly lower in the indobufen group than in the aspirin group (4.1% (3/74) vs. 13.3% (10/75), χ²=4.547, P<0.05). The levels of FIB, D-D, TM and TAFI in the two groups were lower than those before surgery (P<0.05), and there was no statistical significance between the two groups at baseline and post-operation (P>0.05). Conclusion: The efficacy of indobufen combined with clopidogrel in the prevention of 1-year restenosis after coronary artery bypass graft is similar to that of aspirin combined with clopidogrel, but the incidence of adverse reactions is lower, and the safety is higher in patients treated with indobufen combined with clopidogrel compared to aspirin combined with clopidogrel strategy.

Inhibitory effects of lactoferrin on pulmonary inflammatory processes induced by lipopolysaccharide by modulating the TLR4-related pathway.

This study tested the ability of lactoferrin to modulate pulmonary inflammation. To construct in vitro and in vivo inflammatory lung models, cells from the human lung adenocarcinoma cell line (A549) were exposed to lipopolysaccharide (LPS, 1 µg/mL), and mice (CD-1) were intratracheally administered LPS [10 mg/kg of body weight (BW), tracheal lumen injection], respectively. The A549 cells were preincubated with lactoferrin (10 mg/mL), and the mice were intraperitoneally injected with lactoferrin (100 mg/kg of BW), followed by LPS treatment. The concentrations of proinflammatory cytokines (IL-1ß and TNF-α) in culture medium of A549 cells and in bronchoalveolar lavage fluid of the mice were determined using enzyme-linked immunosorbent assays. The toll-like receptor 4-related pathway (TLR4/MyD88/IRAK1/TRAF6/NFκB) was determined at gene and protein expression levels in A549 cells and mouse lung tissue. Results showed that LPS treatment significantly elevated the concentrations of IL-1ß and TNF-α in the A549 cell culture medium and in bronchoalveolar lavage fluid of the mice; it also elevated both the mRNA and protein expressions of TLR4 and the TLR4 downstream factors in A549 cells and mouse lung tissue. Nevertheless, lactoferrin apparently depressed the releases of IL-1ß and TNF-α from A549 cells and lung tissues stimulated by LPS, and significantly suppressed the TLR4 signaling pathway. Lactoferrin also promoted the enhancement of miR-146a expression in A549 cells and mouse lung tissue. Moreover, 100°C heating for 3 min caused total loss of the previously listed bioactivity of lactoferrin. Collectively, we proved that lactoferrin intervened in LPS-induced inflammation in the pulmonary cell model and in the mouse model, through inhibiting the TLR4-related pathway.

[Correlation of damage-associated molecular pattern molecules with age and body mass index].

Objective: To explore the correlation of damage-associated molecular pattern molecules(DAMPs) serum S100, C-reactive protein (CRP), serum amyloid A (SAA) and uric acid (UA) with age and body mass index (BMI) to provide direction for further study of metabolic inflammation and inflammaging. Methods: The observational study method was used,and three hundred and sixty-six healthy people (131 males and 235 females) were selected from the physical examination center of the Second People's Hospital of Hunan Province from May to October 2020. They were divided into three age groups according to the age interval of 20 years, including 156 (53 males and 103 females) aged 20-40 years, 110 (36 males and 74 females) aged 41-60 years, and 100 (42 males and 58 females) aged 61-80 years. Kruskal Wallis H test was used to compare the differences of serum S100, CRP, SAA and UA levels among different age groups. According to the Health Industry Standards of the People's Republic of China-Weight Determination for Adults, the boundary is BMI =24 kg/m2. The healthy people were divided into non overweight (BMI<24 kg/m2) and overweight (BMI ≥ 24 kg/m2) two groups. The 1∶1 propensity score was used to match the age and gender. There were 96 non overweight subjects [43 males, 53 females, age 52 (35, 66) years], 96 overweight subjects [44 males, 52 females, age 52 (36, 64) years]. The serum levels of S100, CRP, SAA and UA in different BMI groups were compared by Mann-Whitney U test. Results: The median serum UA concentrations in males and females were 356 and 277 µmol/L, and the levels of serum UA of male was significantly higher than that of female (Z=-10.428, P<0.001); the median serum SAA concentrations in males and females were 3.1 mg/L and 4.4 mg/L, while the serum SAA level of female was significantly higher than that of male (Z=3.652, P<0.001); for 20-40, 41-60, and 61-80 years old group, the median concentration of serum S100 was 0.058, 0.057, 0.070 µg/L, and the median concentration of serum CRP was 0.32, 0.58, 0.93 mg/L; the median serum SAA concentrations were 3.2, 4.0, 5.2 mg/L; serum uric acid concentrations were (301.8±61.5), (298.6±69.8), (329.0±77.8) µmol/L. The levels of serum S100, CRP, SAA, UA in 61-80 years group were significantly higher than those of 20-40 years group (H=-2.749, H=-6.731, H=-5.033, H=-2.521, P=0.018, P<0.001, P<0.001, P=0.035) and 41-60 years old group (H=-2.719, H=-2.539, H=-2.540, H=-2.486, P=0.020, P=0.033, P=0.033, P=0.039).The levels of serum CRP of 41-60 years group was significantly higher than that of 20-40 years group (H=-4.108,P<0.001). There was no significant difference in levels of serum S100, SAA and UA between 20-40 years group and 41-60 years group (H=0.189, H=-2.360, H=-0.165, P=1.000, P=0.055, P=1.000); the levels of serum CRP and SAA were positively correlated with age (rs =0.342, rs =0.301, P<0.001, P<0.001); for overweight, non-overweight group, the median concentrations of serum S100 were 0.065 µg/L, 0.059 µg/L, the median concentrations of serum CRP were 0.92 mg/L, 0.47 mg/L, the median concentrations of serum SAA were 5.0 mg/L, 4.1 mg/L, the median concentrations of serum UA were 339.5 µmol/L, 301.5 µmol/L, the levels of CRP, SAA and UA in the overweight group were higher than those in the non-overweight group (Z=4.278, Z=2.025, Z=3.787, P<0.001, P=0.043, P<0.001); the levels of S100 in the overweight group was higher than those in the non-overweight group, but there was no significant difference in S100 between the two groups (Z=0.862, P=0.388); the levels of Serum CRP and UA were positively correlated with BMI (rs =0.348, rs =0.264, P<0.001, P=0.009). Conclusions: With the increase of age, the serum S100, CRP, SAA and UA levels of healthy people may be on the rise, especially the serum CRP and SAA levels are positively correlated with age; the serum S100, CRP, SAA and UA levels of overweight people may be higher than those of non-overweight people, especially the serum CRP, UA levels are positively correlated with BMI.

[Screening of biomarkers in exhaled breath of mice exposed to benzene].

Objective: To screen the biomarkers in the exhaled breath of mice exposed to benzene by using exhaled breath online analysis system. Methods: Thirty 8-week-old male C57BL/6 mice were randomly divided into six groups (0, 3, 32, 324, 648, and 1 296 mg/m3) and treated with benzene vapour for 28 days. At the end of the exposure, the peripheral blood cell counts and blood glutathione (GSH) were detected. The content of malondialdehyde (MDA) in HL60 cells treated by mice plasma was examined. Exhaled breath data from mice were collected by Secondary electrospray ionization source high resolution mass spectrometry (SESI-HRMS). Targeted analysis underlying benzene metabolites and oxidative stress metabolites was performed to screen the biomarkers in exhaled breath. Results: After benzene exposure, the number of peripheral blood cells was decreased in different degrees, particularly in the white blood cells (WBC) number. The WBC in 32 and 324 mg/m3 groups was declined by 27.76% and 52.87%, respectively compared to that in control group (P<0.05). Meanwhile, compared with the control group, the GSH content of peripheral blood cells from 324 mg/m3 group decreased by 13.16% (P<0.05). In addition, MDA content was increased by 18.11% in HL60 cells treated with plasma from 324 mg/m3 group mice (P<0.05). The phenol, hydroquinone/catechol, benzenetriol and trans, trans-Muconic acid (t,t-MA) in the exhaled gas of mice could be used as biomarkers for benzene exposure (R2>0.8, P<0.001). The peak intensity of five small molecular metabolites related to oxidative stress (ω-carboxylic fatty acid C5H10O3, ω-carboxylic fatty acid C6H12O3, glutamate, cysteine and MDA) increased with the increase of benzene concentration (P<0.05), which was negatively correlated with WBC decline (P<0.001), suggesting that these molecules mignt be used as biomarkers of benzene-induced toxicity. Conclusions: Phenol, hydroquinone/catechol, benzenetriol and trans, trans-Muconic acid (t,t-MA) in exhaled breath of mice could be used as biomarkers for benzene exposure; ω-carboxylic fatty acid C5H10O3, ω-carboxylic fatty acid C6H12O3, glutamate, cysteine and MDA might be used as markers of benzene-induced toxicity.