One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Objective:To analyze clinical characteristics of Mycoplasma pneumoniae-induced rash and mucositis in children. Methods:Clinical data were collected from children diagnosed with Mycoplasma pneumoniae -induced rash and mucositis in the Department of Dermatology, Capital Center for Children's Health, Captital Medical University from August 1, 2023, to December 1, 2023, and their clinical features were analyzed. Results:A total of 15 children with Mycoplasma pneumoniae-induced rash and mucositis were collected, including 8 males and 7 females, aged 4 to 12 years. They were clinically characterized by obvious mucositis, and skin lesions were relatively mild. Oral mucosal involvement was observed in 13 cases, including lip ulcers (12 cases), oral mucositis (7 cases), tongue ulcers (3 cases), and glossitis (1 case) ; ocular mucosal involvement was reported in 7 cases, including suppurative conjunctivitis (4 cases), and eyelid edema (3 cases) ; 3 children had vulvogenital mucosal involvement, including coronary sulcus ulcers (1 case), urethral meatus ulcers (1 case), labia minora ulcers (1 case), and perianal ulcers (1 case) ; 1 child had nasal mucosal ulcers. Skin lesions occurred on the upper limbs in 5 cases, on the lower limbs in 6 cases, on the face in 2 cases, on the vulva in 2 cases, as well as on the trunk in 1 case. The types of skin lesions included targetoid erythema in 11 cases, vesiculobullous lesions in 6 cases and atypical targetoid erythema in 2 cases. PCR for the detection of Mycoplasma pneumoniae in vesiculobullous fluids showed negative results in the 6 patients with vesiculobullous lesions. The patients received systemic and topical treatment with antibiotic agents and glucocorticoids, as well as supportive therapy. Main pulmonary symptoms as well as skin and mucosal lesions of the 15 children subsided within 3 weeks, and they all had a favorable prognosis, without obvious complications or sequelae. Conclusion:Mycoplasma pneumoniae-related skin and mucosal lesions predominantly present as mucositis, with mild or absent skin involvement. The disorder usually has a mild course, characterized by short disease duration and favorable prognosis.

Objective To detect the serum soluble endothelial factor(sEng)and placental protein 13(PP13)levels on fetal growth restriction(FGR)in patients with early-onset severe preeclampsia(EOSP)and toanalyze the predictive value.Methods A total of 138 EOSP patients admitted to the obstetrics and gynecology department of Department of Obstetrics,Handan Central Hospital from February 2022 to December 2023 were included as the eclampsia group.Patients with FGR were classified as the restricted group(n=72),while those without FGR were classified as the unrestricted group(n=66).49 healthy pregnant women who underwent physical examination at Department of Obstetrics,Handan Central Hospital were regarded as control group.The general information of the eclampsia group was collected and statistically analyzed.ELISA method was applied to detect sEng and PP13 in serum.Pearson correlation was applied to analyze the correlation between serum sEng,PP13 and neonatal weight.Logistic regression model was applied to analyze the influencing factors of FGR in EOSP patients.ROC curve was applied to analyze the value of serum sEng and PP13 in predicting FGR in EOSP patients.Results The serum sEng(39.03±4.02 ng/L)of the eclampsia group was higher than that of the control group(32.75±3.64 ng/L),and PP13(1.20±0.20 μg/L)was lower than that of the control group(1.69±0.28 μg/L),and the differences were statistically significant(t=9.622,13.182,all P<0.05).The systolic blood pressure(172.64±7.52 mmHg),diastolic blood pressure(109.56±3.29 mmHg),24-hour urine protein(1 951.08±210.16 mg/24 h),adverse maternal and infant outcomes(33.33%)and sEng(41.56±4.22 ng/L)in the restricted group were higher than those in the unrestricted group(166.72±5.11 mmHg,106.39±4.88 mmHg,1504.36±164.27 mg/24 h,12.12%,36.28±3.81 ng/L),and neonatal weight(1 864.07±191.33 g),PP13(1.08±0.13 μg/L)was lower than that in the unrestricted group(2437.94±257.81g,1.34±0.27 μg/L),and the differences were statistically significant(t=4.507～14.930,all P<0.05).Serum sEng was negatively correlated with neonatal weight(r=-0.532,P<0.001),while serum PP13 was positively correlated with neonatal weight(r=0.471,P<0.001).High systolic blood pressure,high diastolic blood pressure,high 24-hour urine protein,and high sEng were risk factors for FGR in EOSP patients,while high PP13 was a protective factor(Wald χ2=4.731～129.166,all P<0.05).The AUC(95%CI)predicted by combined detection of serum sEng and PP13 was higher than AUC(95%CI)predicted by single detection and the differences were statistically significant(Z=2.790,3.443,all P<0.05).Conclusion EOSP patients with FGR have higher serum sEng level and lower PP13 level.sEng and PP13 are influencing factors for FGR in EOSP patients.Combined detection can improve the clinical value of predicting FGR in EOSP patients.

We collected the positive serum of Echinococcus granulosus infection in sheep,an inter-mediate host with strong immune response,and used healthy serum as negative control,purified the serum and target protein to capture and enrich the corresponding antigen by immunoprecipita-tion,and obtained target protein-antibody-target protein complex.Mass spectrometry strategies were combined to screen and identify specific antigens associated with Echinococcus granulosus,and the proteins with the highest peptide coverage were analyzed bioinformatically using online prediction software.The results showed that 133 Echinococcus granulosus related proteins were i-dentified by IP-MS.Among them,one protein with peptide coverage≥70％was actin Ⅱ,and three proteins with peptide coverage between 30％to 40％were Ton B box domain containing protein,NADH dehydrogenase(ubiquinone)1 α-subcomplex 2(NADH dehydrogenase[ubiquinone])and lactic dehydrogenase.There were six proteins with 20％to 30％peptide coverage,namely,spli-cing factor 3B subunit 5,tumor protein D52,expressed conserved protein,NADH dehydrogenase(ubiquinone)1 alpha subcomplex 7,inosine-5'-monophosphate dehydrogenase,and aldo keto re-ductase family 1 member B4.Bioinformatics analysis revealed that actin protein has no signal pep-tide,it is probably a non-secretory protein and is subcellularly localized to the cytoskeleton,six op-timal potential antigenic epitopes are present,and the secondary and tertiary structures are consist-ently dominated by α-helices and irregular convolutions.The results indicate that immunoprecipita-tion-mass spectrometry is a high-throughput,simple,rapid and effective method for screening and identifying fine-grained Echinococcus granulosus antigens,which can provide a basis for screening specific molecules for serodiagnostic markers in intermediate host sheep and for the development of novel diagnostic techniques for hydatid diseases.

Objective:To analyze clinical characteristics of Mycoplasma pneumoniae-induced rash and mucositis in children. Methods:Clinical data were collected from children diagnosed with Mycoplasma pneumoniae -induced rash and mucositis in the Department of Dermatology, Capital Center for Children's Health, Captital Medical University from August 1, 2023, to December 1, 2023, and their clinical features were analyzed. Results:A total of 15 children with Mycoplasma pneumoniae-induced rash and mucositis were collected, including 8 males and 7 females, aged 4 to 12 years. They were clinically characterized by obvious mucositis, and skin lesions were relatively mild. Oral mucosal involvement was observed in 13 cases, including lip ulcers (12 cases), oral mucositis (7 cases), tongue ulcers (3 cases), and glossitis (1 case) ; ocular mucosal involvement was reported in 7 cases, including suppurative conjunctivitis (4 cases), and eyelid edema (3 cases) ; 3 children had vulvogenital mucosal involvement, including coronary sulcus ulcers (1 case), urethral meatus ulcers (1 case), labia minora ulcers (1 case), and perianal ulcers (1 case) ; 1 child had nasal mucosal ulcers. Skin lesions occurred on the upper limbs in 5 cases, on the lower limbs in 6 cases, on the face in 2 cases, on the vulva in 2 cases, as well as on the trunk in 1 case. The types of skin lesions included targetoid erythema in 11 cases, vesiculobullous lesions in 6 cases and atypical targetoid erythema in 2 cases. PCR for the detection of Mycoplasma pneumoniae in vesiculobullous fluids showed negative results in the 6 patients with vesiculobullous lesions. The patients received systemic and topical treatment with antibiotic agents and glucocorticoids, as well as supportive therapy. Main pulmonary symptoms as well as skin and mucosal lesions of the 15 children subsided within 3 weeks, and they all had a favorable prognosis, without obvious complications or sequelae. Conclusion:Mycoplasma pneumoniae-related skin and mucosal lesions predominantly present as mucositis, with mild or absent skin involvement. The disorder usually has a mild course, characterized by short disease duration and favorable prognosis.

Objective To detect the serum soluble endothelial factor(sEng)and placental protein 13(PP13)levels on fetal growth restriction(FGR)in patients with early-onset severe preeclampsia(EOSP)and toanalyze the predictive value.Methods A total of 138 EOSP patients admitted to the obstetrics and gynecology department of Department of Obstetrics,Handan Central Hospital from February 2022 to December 2023 were included as the eclampsia group.Patients with FGR were classified as the restricted group(n=72),while those without FGR were classified as the unrestricted group(n=66).49 healthy pregnant women who underwent physical examination at Department of Obstetrics,Handan Central Hospital were regarded as control group.The general information of the eclampsia group was collected and statistically analyzed.ELISA method was applied to detect sEng and PP13 in serum.Pearson correlation was applied to analyze the correlation between serum sEng,PP13 and neonatal weight.Logistic regression model was applied to analyze the influencing factors of FGR in EOSP patients.ROC curve was applied to analyze the value of serum sEng and PP13 in predicting FGR in EOSP patients.Results The serum sEng(39.03±4.02 ng/L)of the eclampsia group was higher than that of the control group(32.75±3.64 ng/L),and PP13(1.20±0.20 μg/L)was lower than that of the control group(1.69±0.28 μg/L),and the differences were statistically significant(t=9.622,13.182,all P<0.05).The systolic blood pressure(172.64±7.52 mmHg),diastolic blood pressure(109.56±3.29 mmHg),24-hour urine protein(1 951.08±210.16 mg/24 h),adverse maternal and infant outcomes(33.33%)and sEng(41.56±4.22 ng/L)in the restricted group were higher than those in the unrestricted group(166.72±5.11 mmHg,106.39±4.88 mmHg,1504.36±164.27 mg/24 h,12.12%,36.28±3.81 ng/L),and neonatal weight(1 864.07±191.33 g),PP13(1.08±0.13 μg/L)was lower than that in the unrestricted group(2437.94±257.81g,1.34±0.27 μg/L),and the differences were statistically significant(t=4.507～14.930,all P<0.05).Serum sEng was negatively correlated with neonatal weight(r=-0.532,P<0.001),while serum PP13 was positively correlated with neonatal weight(r=0.471,P<0.001).High systolic blood pressure,high diastolic blood pressure,high 24-hour urine protein,and high sEng were risk factors for FGR in EOSP patients,while high PP13 was a protective factor(Wald χ2=4.731～129.166,all P<0.05).The AUC(95%CI)predicted by combined detection of serum sEng and PP13 was higher than AUC(95%CI)predicted by single detection and the differences were statistically significant(Z=2.790,3.443,all P<0.05).Conclusion EOSP patients with FGR have higher serum sEng level and lower PP13 level.sEng and PP13 are influencing factors for FGR in EOSP patients.Combined detection can improve the clinical value of predicting FGR in EOSP patients.

We collected the positive serum of Echinococcus granulosus infection in sheep,an inter-mediate host with strong immune response,and used healthy serum as negative control,purified the serum and target protein to capture and enrich the corresponding antigen by immunoprecipita-tion,and obtained target protein-antibody-target protein complex.Mass spectrometry strategies were combined to screen and identify specific antigens associated with Echinococcus granulosus,and the proteins with the highest peptide coverage were analyzed bioinformatically using online prediction software.The results showed that 133 Echinococcus granulosus related proteins were i-dentified by IP-MS.Among them,one protein with peptide coverage≥70％was actin Ⅱ,and three proteins with peptide coverage between 30％to 40％were Ton B box domain containing protein,NADH dehydrogenase(ubiquinone)1 α-subcomplex 2(NADH dehydrogenase[ubiquinone])and lactic dehydrogenase.There were six proteins with 20％to 30％peptide coverage,namely,spli-cing factor 3B subunit 5,tumor protein D52,expressed conserved protein,NADH dehydrogenase(ubiquinone)1 alpha subcomplex 7,inosine-5'-monophosphate dehydrogenase,and aldo keto re-ductase family 1 member B4.Bioinformatics analysis revealed that actin protein has no signal pep-tide,it is probably a non-secretory protein and is subcellularly localized to the cytoskeleton,six op-timal potential antigenic epitopes are present,and the secondary and tertiary structures are consist-ently dominated by α-helices and irregular convolutions.The results indicate that immunoprecipita-tion-mass spectrometry is a high-throughput,simple,rapid and effective method for screening and identifying fine-grained Echinococcus granulosus antigens,which can provide a basis for screening specific molecules for serodiagnostic markers in intermediate host sheep and for the development of novel diagnostic techniques for hydatid diseases.

Objective:To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL).Methods:A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children′s Hospital, Capital Medical University and Baoding Children′s Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients.Results:Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) ( χ2=1.88, 1.47, P=0.170, 0.224). Conclusions:Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

Objective:To analyze the risk factors that affect the prognosis of patients with hypopharyngeal squamous cell carcinoma（HPSCC） and to compare the efficacy of surgical resection followed by adjuvant radiotherapy（SR） with that of neoadjuvant therapy consisting of platinum-based chemotherapy and fluorouracil combined with either cetuximab or nimotuzumab, followed by SR. The study also aimed to evaluate the overall survival（OS） of patients, their postoperative eating function, tracheostomy decannulation rate, and tumor response to the two neoadjuvant chemotherapies. Methods:A retrospective analysis was performed on the medical records of HPSCC patients who received SR or neoadjuvant therapy followed by SR treatment at the Shanghai General Hospital from 2012 to 2019 and had not undergone any prior treatment. The prognostic factors were analyzed, and the survival analysis of patients who underwent SR treatment with two neoadjuvant chemotherapy regimens was performed. Results:A total of 108 patients were included in the study. The results of the univariate analysis showed that gender（P=0.850） had no significant correlation with the survival rate of HPSCC patients who underwent SR. However, age, smoking history, alcohol consumption history, platelet-to-lymphocyte ratio（PLR）, neutrophil-to-lymphocyte ratio（NLR）, T stage, N stage, neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil, and histological grade were significantly associated with prognosis（P<0.05）. The multivariate analysis revealed that smoking history, histological grade, and neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil were independent risk factors affecting the prognosis of HPSCC（P<0.05）. Patients who received neoadjuvant therapy had longer OS than those who underwent SR only（P<0.001）. There was no significant difference in tumor response to the two neoadjuvant therapies and in OS（P>0.05）, and there was no significant difference in the rate of oral feeding and tracheostomy decannulation among the three treatment groups（P>0.05）. Conclusion:Univariate analysis showed that age at tumor onset, smoking history, alcohol consumption history, NLR, PLR, T stage, N stage, whether receiving neoadjuvant chemotherapy, and pathological grade were associated with the prognosis of HPSCC patients receiving SR treatment. Multivariate analysis showed that smoking history, pathological grade, and neoadjuvant chemotherapy were independent risk factors affecting the prognosis. Neoadjuvant chemotherapy with cetuximab or nimotuzumab can prolong the OS of patients, providing a certain basis and reference for the treatment of HPSCC.
Humans ; Neoadjuvant Therapy ; Squamous Cell Carcinoma of Head and Neck ; Cetuximab/therapeutic use* ; Retrospective Studies ; China ; Prognosis ; Fluorouracil ; Head and Neck Neoplasms

Objective:To explore the rapid evaluation of the early pathogen of severe Chlamydophila psittaci pneumonia by bedside diagnostic bronchoscopy, so as to start effective anti-infection treatment before the results of macrogenome next generation sequencing (mNGS) test. Methods:The clinical data of three patients with severe Chlamydophila psittaci pneumonia who were successfully treated in the First Affiliated Hospital of Xinjiang Medical University, the First People's Hospital of Aksu District, and the First Division Hospital of Xinjiang Production and Construction Corps from October 2020 to June 2021 were retrospectively analyzed, including the rapid assessment of early pathogens by bedside diagnostic bronchoscopy and the use of antibiotics to start anti-infection treatment. These patients were successfully treated. Results:The three patients were male, aged 63, 45 and 58 years old, respectively. Before the onset of the penumonia, they had a clear medical history of bird exposure. The clinical manifestations mainly included fever, dry cough, shortness of breath and dyspnea. One case had abdominal pain and lethargy. The results of laboratory examination indicated that the peripheral blood white blood cell count (WBC) of two patients were high [(10.2-11.9)×10 9/L], the percentage of neutrophils increased (85.2%-94.6%) and the percentage of lymphocytes decreased (3.2%-7.7%) in all 3 patients after admission to hospital and entering into intensive care unit (ICU). The procalcitonin (PCT) of 3 patients increased after admission, and still increased when entering ICU (0.3-4.8 ng/L), so did C-reactive protein (CRP, 58.0-162.0 mg/L) and erythrocyte sedimentation rate (ESR, 36.0-90.0 mm/1 h). After admission, serum alanine transaminase (ALT) increased in 2 cases (136.7 U/L, 220.5 U/L), so did aspartate transaminase (AST) in 2 cases (249.6 U/L, 164.2 U/L). ALT (162.2-267.9 U/L) and AST (189.8-223.2 U/L) increased in 3 patients when they entered ICU. The level of serum creatinine (SCr) of 3 patients were normal after admission and entering ICU. The chest computed tomography (CT) findings of 3 patients were acute interstitial pneumonia, bronchopneumonia and lung consolidation, of which 2 cases were accompanied by a small amount of pleural effusion, and 1 case was accompanied by more regular small air sacs. Multiple lung lobes were involved, but mainly one lung lobe. The oxygenation index (PaO 2/FiO 2) of the 3 patients admitting to ICU were 100.0, 57.5 and 105.4 mmHg (1 mmHg ≈ 0.133 kPa), respectively, which met with the diagnostic criteria of moderate and severe acute respiratory distress syndrome (ARDS). All three patients received endotracheal intubation and mechanical ventilation. Under the bedside bronchoscope, the bronchial mucosa of 3 patients were obviously congested and edematous, without purulent secretion, and there was 1 case with mucosal hemorrhage. Three patients underwent bedside diagnostic bronchoscopy, and the evaluation result of the pathogen was that it might be atypical pathogen infection, so they were given moxifloxacin, cisromet and doxycycline intravenously, respectively, and combined with carbapenem antibiotics intravenously. After 3 days, the detection results of mNGS in bronchoalveolar lavage fluid (BALF) showed that only Chlamydia psittaci was infected. At this time, the condition was significantly improved, and PaO 2/FiO 2 was significantly increased. Therefore, the antibiotic treatment scheme remained unchanged, and mNGS only served to verify the initial diagnosis. Two patients were extubated on the 7th and 12th day of admission to the ICU, respectively, while one patient was extubated on the 16th day of admission to the ICU due to nosocomial infection. All 3 patients were transferred to the respiratory ward after the condition was stable. Conclusion:The bedside diagnostic bronchoscopy based on clinical characteristics is conducive to not only the rapid assessment of the early pathogens of severe Chlamydia psittaci pneumonia, but also effective anti-infection treatment before the returning of mNGS test results, which can make up for the lag and uncertainty of the mNGS test results.