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

As the search for effective treatments for COVID-19 continues, the high mortality rate among critically ill patients in Intensive Care Units (ICU) presents a profound challenge. This study explores the potential benefits of traditional Chinese medicine (TCM) as a supplementary treatment for severe COVID-19. A total of 110 critically ill COVID-19 patients at the Intensive Care Unit (ICU) of Vulcan Hill Hospital between Feb., 2020, and April, 2020 (Wuhan, China) participated in this observational study. All patients received standard supportive care protocols, with a subset of 81 also receiving TCM as an adjunct treatment. Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed. Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group (16 of 81 vs 24 of 29; 0.3 vs 2.3 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with improved survival odds (P < 0.001). Furthermore, the analysis also revealed that TCM treatment could partially mitigate inflammatory responses, as evidenced by the reduced levels of proinflammatory cytokines, and contribute to the recovery of multiple organic functions, thereby potentially increasing the survival rate of critically ill COVID-19 patients.
Humans ; COVID-19 ; Medicine, Chinese Traditional ; SARS-CoV-2 ; Critical Illness ; Treatment Outcome

Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost, sustainability, and tissue targeting. Thus, they hold promise for disease treatment and drug delivery. In this study, we proposed a time-efficient method, PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles (GDNVs). Subsequently, curcumin (CUR) was loaded onto GDNV by ultrasonic incubation. The optimum conditions for ginger-derived nanovesicles loaded with curcumin (CG) were ultrasound time of 3 min, a carrier-to-drug ratio (GDNV:CUR) of 1:1. The study achieved a high loading capacity (94.027% ± 0.094%) and encapsulation efficiency (89.300% ± 0.344%). Finally, the drugs' in vivo distribution and anti-colitis activity were investigated in mice. CG was primarily distributed in the colon after oral administration. Compared to CUR and GDNV, CG was superior in improving disease activity, colon length, liver and spleen coefficients, myeloperoxidase activity, and biochemical factor levels in ulcerative colitis (UC) mice. In addition, CG plays a protective role against UC by modulating serum metabolite levels and gut flora. In summary, our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.

Objective:To evaluate the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) with or without ribavirin in the treatment of patients diagnosed with chronic hepatitis C (CHC) and chronic kidney disease (CKD).Methods:From June 2018 to May 2022, a total of 75 patients with CHC and CKD, and treated with SOF/VEL±ribavirin at the Kunming Third People′s Hospital were enrolled in this study. The basic information of patients were collected. Assessments of renal function, liver function, virologic response rate and adverse events were conducted at baseline, four weeks and 12 weeks of treatment and 12 weeks after treatment withdrawal. Wilcoxon rank sum test and Kruskal-Wallis rank sum test were used for statistical analysis.Results:Among the 75 patients, 51 cases(68.0%) were classified as CKD stage 2, 12 cases (16.0%) as CKD stage 3, four cases (5.3%) as CKD stage 4, eight cases (10.7%) as CKD stage 5. Additionally, 26 cases (34.7%) were classified as HCV type 3a, while 37 cases (49.3%) were classified as type 3b. Among the patients, 51 cases (68.0%) had cirrhosis, including 15(20.0%) compensated cirrhosis and 36(48.0%) decompensated cirrhosis. Twelve weeks after treatment withdrawal, there was a statistically significant improvement in the estimated glomerular filtration rate (eGFR) compared to baseline (81.76(60.94, 94.34) mL/(min·1.73 m 2) vs 70.99(52.86, 82.38) mL/(min·1.73 m 2), Z=8.12, P=0.040). From baseline to 12 weeks after treatment withdrawal, eGFR of patients with CKD stage 2 and stage 3 were both gradually increased, with statistical significance ( H=8.91 and 8.03, respectively, both P<0.05). For CKD stage 2 patients, eGFR increased from 78.82(70.98, 84.80) mL/(min·1.73 m 2) to 86.94 (75.91, 96.01) mL/(min·1.73 m 2), while CKD stage 3 patients had an increased from 51.24 (45.92, 53.37) mL/(min·1.73 m 2) to 64.58 (44.54, 74.34) mL/(min·1.73 m 2). Renal function was improved to CKD stage 1 in 21 patients (28.0%). Compared to baseline, CKD stage 2 patients exhibited a decrease of aspartate aminotransferase to platelet ratio index 12 weeks after treatment withdrawal, and alanine aminotransferase and aspartate aminotransferase levels were also significantly improved with statistical significance ( Z=8.03, 21.57 and 43.74, respectively, all P<0.05). The rate of sustained virological response (SVR)12 at 12 weeks after treatment withdrawal was 98.7%(74/75). Among these cases, 51 patients in CKD stage 2, 11 patients in CKD stage 3, 12 patients in CKD stage 4 and stage 5 reached SVR12. Adverse events occurred in 32 patients (42.7%), including 18 cases of mild hemolytic anemia, four cases of skin itching, three cases of rash, two cases of chest tightness, and five cases of fatigue. Conclusions:SOF/VEL with or without ribavirin for the treatment of patients with CHC and CKD has good effectiveness and safety. The renal function, liver function and liver fibrosis degree have been improved after antiviral treatment.

Objective:To explore the effect of educational intervention based on timing theory on mothers of premature infants.Methods:Using the convenience sampling method, 80 mothers of premature infants hospitalized in the Neonatology Department of Affiliated Hospital of Youjiang Medical University for Nationalities from May 2019 to October 2020 were included in this study. According to the time of admission, they were divided into the control group (42 cases) and the observation group (38 cases). The mothers in the control group were given routine educational guidance during the hospitalization of premature infants, while the mothers in the observation group were given comprehensive educational intervention based on timing theory on the basis of the control group. The mothers′ caring ability during the transition period, breastfeeding self-efficacy and breastfeeding rate at a month after discharge, and mother′s coping ability at 3 months after discharge were compared between the two groups.Results:There were 35 cases in each group completed the study. The observation group scored (100.86 ± 6.22) on the maternal care ability of premature infants in transition period, and the control group scored (89.51 ± 4.17), the difference between the two groups was statistically significant ( t=-8.97, P<0.05). The breastfeeding self-efficacy score of the observation group a month after discharge from hospital was (47.83 ± 2.54) points, which was higher than (41.20 ± 1.97) points of the control group, and the difference was statistically significant ( t=-12.21, P<0.05). The breastfeeding rate a month after discharge in the observation group was 62.9% (22/35), which was higher than 37.1% (13/35) in the control group, and the difference was statistically significant ( χ2=4.63, P<0.05). The maternal coping ability scores of the premature infants in the observation group and control group 3 months after discharge were (119.29 ± 6.03) and (113.66 ± 6.59) points respectively, and the difference between the two groups was statistically significant ( t=-3.73, P<0.05). Conclusions:The educational intervention based on timing theory can help mothers of premature infants master the nursing knowledge and skills, strengthen the mother′s transitional care ability and post-discharge coping ability, improve the breastfeeding self-efficacy and breastfeeding rate of premature infants, promote and development the growth of premature infants, worthy of clinical application.

Objective:To study the genetic profile of neonatal hyperbilirubinemia with unknown etiology in Guangdong Province and the clinical significance of jaundice-related genetic screening.Methods:From July to September, 2021, neonates with hyperbilirubinemia of unknown etiology born in different hospitals in Guangdong Province were studied. 24 neonatal jaundice-related exons were sequenced using targeted capture and high-throughput sequencing technology. The pathogenic variants were analyzed.Results:A total of 331 cases, 139 (42.0%) cases showed positive screening results with five diseases, including 65 (19.6%) cases of Gilbert syndrome, 48 (14.5%) cases of glucose-6-phosphate dehydrogenase (G6PD) deficiency,18 (5.4%) cases of sodium taurocholate cotransporting polypeptide deficiency, 4 (1.2%) cases of Citrin deficiency and 4 (1.2%) cases of Dubin-Johnson syndrome. 149 (45.0%) cases carried one or more genetic variants and 43 (13.0%) cases showed no clinically significant variants. The 8 high-frequency mutation loci (carrier rate >1%) are UGT1A1 gene c.211G>A and c.1091C>T, G6PD gene c.1466G>T and c.1478G>A, SLC10A1 gene c.800C>T, SLC25A13 gene c.852_855del TATG, HBB gene c.126_129delCTTT and c.316-197C>T.Conclusions:Genetic factors are important for neonatal hyperbilirubinemia with unknown etiology in Guangdong. The common pathogenic genes are UGT1A1, G6PD, SLC10A1, and SLC25A13 and the population carries high-frequency mutation loci. Therefore, genetic screening in neonates with hyperbilirubinemia of unknown etiology has important clinical significance.

Objective:To summarize the clinical features and pathological changes of peripheral tissues from patients with neuronal intranuclear inclusion disease (NIID) diagnosed by genetic tests.Methods:Repeat-primed polymerase chain reaction was used to confirm the GGC repeated expansion in the 5′ untranslated region of the NOTCH2NLC gene in patients with suspected NIID who had visited the Department of Neurology of Peking University First Hospital from January 2018 to February 2020. The clinical data and pathological changes of peripheral tissues from patients with genetically diagnosed NIID were collected retrospectively and analysed. Immunostaining with anti-p62 and anti-ubiquitin antibody was performed on peripheral biopsy specimens.Results:Totally nine patients with NIID who had GGC repeated expansion in the NOTCH2NLC gene were found. Five patients were familial (from three faimilies), and four patients were sporadic. The age of onset was 36-61(51.33±7.12) years. The most common symptoms in this NIID group were episodic emotion and personality change (8/9), paroxysmal disturbance of consciousness (6/9) and intermitant head discomfort (6/9). Other symptoms included cognitive dysfunction, limb weakness, limb sensory disturbance, bladder dysfunction, ataxia, seizures and psychiatric symptoms. Brain magnetic resonance imaging showed high signals along the corticomedullary junction on diffusion-weighted image in eight out of nine patients. Skin biopsied samples from nine patients demonstrated the presence of eosinophilic intranuclear inclusions (IIs), appearing in the nucleus of fibroblasts, fat cells and ductal epithelial cells of sweat glands on hematoxylin-eosin staining. IIs were positive on anti-p62 and anti-ubiquitin immunostaining. Electron microscopy indicated the IIs were composed of a pile of filament materials without membrane. Muscle biopsies from two patients showed no obvious neurogenic or myogenic pathologic changes, except in one patient several rimmed vacuoles fibers were found. In one patient sural nerve biopsy showed severe demyelinating pathological changes. No IIs were found in the muscles and peripheral nerve tissue either by histological examination or by immunohistochemical staining with anti-p62 or anti-ubiquitin, while IIs were found by immunofluorescence staining with both anti-p62 and anti-ubiquitin in three patient′s tissue. Conclusions:The phenotype of this NIID patient group is adult-onset NIID, with episodic encephalopathy as the main clinical manifestation. Skin biopsy has high pathological diagnostic value for NIID. The immunofluorescence staining with anti-p62 and anti-ubiquitin is easier to detect the presence of IIs than histological staining and immumohistochemical staining.

Objective:To build a performance evaluation index system of family doctor contracting service for urban communities, so as to evaluate the effects of such service.Methods:Based on the conceptual framework of performance appraisal of family doctor contracting service, such means as Delphi method and analytic hierarchy process were employed to evaluate the performance appraisal system of such service. A measured simulation test was made in Guangzhou.Results:A library of performance appraisal candidate indexes for such service was established, based on the performance appraisal concept framework of " structure, input, output, result" of such service. A questionnaire made based on such a library was developed for correspondence inquiry of 20 experts from December 2018 to June 2019. Based on results of such inquiry, a performance appraisal system for family doctor contracting service in Guangzhou was developed, consisting of 4 level-1 indexes, 10 level-2 indexes and 34 level-3 indexes. In the system, level indexes include organizational structure and management(weight 0.21), resource input(weight 0.24), contracting service process(weight 0.19), and contracting service effect(weight 0.36). A community health center in Guangzhou was used as the measurement site, for adjustment and improvement of data acquisition methods of individual indexes or scoring criteria.Conclusions:The index system is developed scientifically; appraisal tools are designed focusing on results and outputs, ensuring the appraisal of contracting service quality from multiple perspectives of supply-demand sides and health management patterns; the system can provide appraisal tools for policy appraisal authorities to evaluate the performance of contracting service reform.

Objective:To investigate the clinical significance of inflammatory factors in bacterial infection children with glucose-6-phosphate dehydrogenase (G6PD) deficiency in PICU.Methods:A prospective cohort study was carried out from June 2014 to December 2017. 77 bacterial infection children with pediatric critical illness score less than 80 who were admitted to the PICU, were recruit in the study.The patient diagnosed as other basic diseases,with history of high-dose glucocorticoid use, discharged or died within 24 hours were excluded.The recruited patients were divided into G6PD deficiency group (observation group with 36 cases) and non-G6PD deficiency group (control group with 41 cases) according to the presence or absence of G6PD deficiency.Blood samples were taken at admission, 12 hand 24 h after hospitalization to detect the concentrations of tumor necrosis factor (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10) andC-reactive protein (CRP). T test, χ2 test and Fisher exact test were used to analyze the changes of the above inflammatory factors, complications, prognosis, PICU stay time and hospitalization costs. Results:The levels of inflammatory factors in the observation group were significantly higher than those in the control group at admission, 12 and 24 hours after hospitalization, the differences were statistically significant (all P< 0.05). There was no statistically significant difference in thechangerate of inflammatory factors between the two groups during treatment; The PICU stay time of observation group was longer [(7.98 ± 6.55) vs (5.01 ± 6.21)] and the hospitalization cost (yuan) was higher [(36 634.09 ± 11 876.67) vs (31 571.42 ± 10 245.80)], P<0.05; Compared to the control group, the incidence ofsevere sepsis, septic shock, MODS increased significantly, and the curative rate decreasedsignificantly in observation group( P<0.05). Conclusions:G6PD-deficient children with bacterial infections had serious inflammatory reactions with poor prognosis and higher hospitalization costs and were susceptible to the occurrence of severe sepsis, septic shock and MODS.

Objective:To explore the serum levels of inflammatory cytokines and prognosis in severe acute infection children with glucose-6-phosphate dehydrogenase(G6PD) deficiency.Methods:A total number of 160 children with severe acute infections admitted to PICU of Guangxi Zhuang Autonomous Region Maternal and Child Health Hospital from June 2014 to December 2017 were selected as subjects in this study, including 80 children with G6PD deficiency(observation group) and 80 children without G6PD deficiency(control group). The changes of TNF-α, IL-6, IL-10 and CRP were dynamically monitored at 0-hour, 12-hour and 24-hour after admision, and the occurrences of sepsis, multiple organ dysfunction syndrome(MODS) were prospectively analyzed.Results:The levels of serum cytokines and CRP in the observation group were significantly higher than those in the control group at admission[TNF-α: (65.57±19.09) pg/ml vs.(46.53±20.34) pg/ml; IL-6: (98.90±29.02) pg/ml vs.(89.89±25.54) pg/ml; IL-10: (87.66±21.84) pg/ml vs.(76.34±19.01) pg/ml; CRP: (60.18±22.24) mg/L vs.(41.43±19.51) mg/L, respectively], and the differences between two groups were statistically significant( P<0.05). The levels of cytokines and CRP in the observation group were higher than those in the control group at 12 h and 24 h after treatment( P<0.01). Compared with the control group, the incidences of sepsis(82.50% vs 67.50%) and MODS(73.75% vs 58.75%) in the observation group increased, and the recovery rate(81.25% vs 92.50%) decreased, with statistical significance between two groups( P<0.05). Conclusion:Children with G6PD deficiency need to be paid more attention to inflammation, sepsis, MODS and the difficulty of treatment when they are infected.The potential mechanism may be related to oxidative stress.