Alzheimer-like behavior and synaptic dysfunction in 3 × Tg-AD mice are reversed with calcineurin inhibition.

Alzheimer's disease is a progressive neurodegenerative disorder characterized by impairments in synaptic plasticity and cognitive performance. Current treatments are unable to achieve satisfactory therapeutic effects or reverse the progression of the disease. Calcineurin has been implicated as part of a critical signaling pathway for learning and memory, and neuronal calcineurin may be hyperactivated in AD. To investigate the effects and underlying mechanisms of FK506, a calcineurin inhibitor, on Alzheimer-like behavior and synaptic dysfunction in the 3 × Tg-AD transgenic mouse model of Alzheimer's disease, we investigated the effect of FK506 on cognitive function and synaptic plasticity in the 3 × Tg-AD transgenic mouse model of Alzheimer's disease. The results showed that FK506 treatment ameliorated cognitive deficits, as indicated by the decreased latency in the water maze, and attenuated tau hyperphosphorylation in 3 × Tg-AD mice. Treatment with FK506 also reduced the levels of certain markers of postsynaptic deficits, including PSD-95 and NR2B, and reversed the long-term potentiation deficiency and dendritic spine impairments in 3 × Tg-AD mice. These findings suggest that treatment with calcineurin inhibitors such as FK506 can be an effective therapeutic strategy to rescue synaptic deficit and cognitive impairment in familial Alzheimer's disease and related tauopathies.

Specific convulsions and brain damage in children hospitalized for Omicron BA.5 infection: an observational study using two cohorts.

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

Synthesis and Antimicrobial Activity Evaluation of Pyridine Derivatives Containing Imidazo[2,1-b][1,3,4]Thiadiazole Moiety.

Four series of novel pyridine derivatives (17 a-i, 18 a-i, 19 a-e, and 20 a-e) were synthesized and their antimicrobial activities were evaluated. Of all the target compounds, almost half target compounds showed moderate or high antibacterial activity. The 4-F substituted compound 17 d (MIC=0.5 µg/mL) showed the highest antibacterial activity, its activity was twice the positive control compound gatifloxacin (MIC=1.0 µg/mL). For fungus ATCC 9763, the activities of compounds 17 a and 17 d are equivalent to the positive control compound fluconazole (MIC=8 µg/mL). Furthermore, compounds 17 a and 17 d showed little cytotoxicity to human LO2 cells, and did not show hemolysis even at ultra-high concentration (200 µM). The results indicate that these compounds are valuable for further development as antibacterial and antifungal agents.

TGF-ß1 inhibitor P144 protects against benign restenosis after esophageal stenting through TGF-ß1/Smads signaling pathway inhibition.

BACKGROUND AND STUDY AIMS: Esophageal restenosis is a serious complication after esophageal stent placement, which influences the clinical prognosis of stent implantation and the patient's quality of life. TGF-ß1/Smads signaling pathway plays an important role in the development of the eosinophilic esophagitis and scar repair after skin trauma. However, the role of TGF-ß1/Smads in the development of esophageal restenosis after esophageal stent placement remains unknown. Our study aimed to investigate whether TGF-ß1/Smads plays an important role in the development of esophageal restenosis after esophageal stent, and whether the exogenous TGF-ß1 inhibitor supplement could ameliorate the esophageal restenosis after esophageal stent. MATERIAL AND METHODS: We established the model of esophageal restenosis after esophageal stenting in rats, and determined the expression levels of TGF-ß1/Smads signaling pathway and the relevant markers of fibroblast activation by immunochemistry (IHC), Western Blot and real time qPCR. Those all the indicators were also determined in esophageal fibroblast when exposed to rhTGF-ß1 with or without TGF-ß1 inhibitor P144. RESULTS: The serum level of IL-1ß and TNFα were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. The TGF-ß1/Smads signaling pathway and the relevant markers of fibroblast activation were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. Those all the indicators were significantly increased when exposed to rhTGF-ß1, and obviously decreased when treated with P144. CONCLUSIONS: TGF-ß1 Inhibitor P144 could protect against benign restenosis after esophageal stenting by down-regulating the expression levels of relevant markers of fibroblast activation through TGF-ß1/Smads signaling pathway inhibition, and may be used as a novel therapy for benign restenosis after esophageal stenting.

Molecular Engineering of Perylene Diimide Polymers with a Robust Built-in Electric Field for Enhanced Solar-Driven Water Splitting.

The built-in electric field of the polymer semiconductors could be regulated by the dipole moment of its building blocks, thereby promoting the separation of photogenerated carriers and achieving efficient solar-driven water splitting. Herein, three perylene diimide (PDI) polymers, namely oPDI, mPDI and pPDI, are synthesized with different phenylenediamine linkers. Notably, the energy level structure, light-harvesting efficiency, and photogenerated carrier separation and migration of polymers are regulated by the orientation of PDI unit. Among them, oPDI enables a large dipole moment and robust built-in electric field, resulting in enhanced solar-driven water splitting performance. Under simulated sunlight irradiation, oPDI exhibits the highest photocurrent of 115.1 µA cm-2 for photoelectrochemical oxygen evolution, which is 11.5 times that of mPDI, 26.8 times that of pPDI and 104.6 times that of its counterparts PDI monomer at the same conditions. This work provides a strategy for designing polymers by regulating the orientation of structural units to construct efficient solar energy conversion systems.

Subchondral fatigue fracture of the femoral head in young military recruits: Potential risk factors.

BACKGROUND: Subchondral fatigue fracture of the femoral head (SFFFH) mainly occurs in young military recruits and might be confused with osteonecrosis of the femoral head. However, less research focuses on the risk factor for SFFFH. AIM: To evaluate the intrinsic risk factors for SFFFH in young military recruits. METHODS: X-ray and magnetic resonance imaging data were used for analysis. Acetabular anteversion of the superior acetabulum, acetabular anteversion of the center of the acetabulum (AVcen), anterior acetabular sector angle (AASA), posterior acetabular sector angle, superior acetabular sector angle, neck-shaft angle (NSA), inferior iliac angle (IIA), and ischiopubic angle were calculated. Then, logistic regression, receiver operating characteristic curve analysis, and independent samples t-test were performed to identify the risk factors for SFFFH. RESULTS: Based on the results of logistic regression, age [odds ratio (OR): 1.33; 95% confidence interval (95%CI): 1.12-1.65; P = 0.0031] and treatment timing (OR: 0.86; 95%CI: 0.75-0.96; P = 0.015) could be considered as the indicators for SFFFH. AVcen (P = 0.0334), AASA (P = 0.0002), NSA (P = 0.0007), and IIA (P = 0.0316) were considered to have statistical significance. Further, AVcen (OR: 1.41; 95%CI: 1.04-1.95) and AASA (OR: 1.44; 95%CI: 1.21-1.77), especially AASA (area under curve: 66.6%), should be paid much more attention due to the higher OR than other indicators. CONCLUSION: We have for the first time unveiled that AASA and age could be key risk factors for SFFFH, which further verifies that deficient anterior coverage of the acetabulum might be the main cause of SFFFH.

NRF2 Deficiency Attenuates Diabetic Kidney Disease in Db/Db Mice via Down-Regulation of Angiotensinogen, SGLT2, CD36, and FABP4 Expression and Lipid Accumulation in Renal Proximal Tubular Cells.

The role(s) of nuclear factor erythroid 2-related factor 2 (NRF2) in diabetic kidney disease (DKD) is/are controversial. We hypothesized that Nrf2 deficiency in type 2 diabetes (T2D) db/db mice (db/dbNrf2 knockout (KO)) attenuates DKD progression through the down-regulation of angiotensinogen (AGT), sodium-glucose cotransporter-2 (SGLT2), scavenger receptor CD36, and fatty -acid-binding protein 4 (FABP4), and lipid accumulation in renal proximal tubular cells (RPTCs). Db/dbNrf2 KO mice were studied at 16 weeks of age. Human RPTCs (HK2) with NRF2 KO via CRISPR-Cas9 genome editing and kidneys from patients with or without T2D were examined. Compared with db/db mice, db/dbNrf2 KO mice had lower systolic blood pressure, fasting blood glucose, kidney hypertrophy, glomerular filtration rate, urinary albumin/creatinine ratio, tubular lipid droplet accumulation, and decreased expression of AGT, SGLT2, CD36, and FABP4 in RPTCs. Male and female mice had similar results. NRF2 KO attenuated the stimulatory effect of the Nrf2 activator, oltipraz, on AGT, SGLT2, and CD36 expression and high-glucose/free fatty acid (FFA)-stimulated lipid accumulation in HK2. Kidneys from T2D patients exhibited markedly higher levels of CD36 and FABP4 in RPTCs than kidneys from non-diabetic patients. These data suggest that NRF2 exacerbates DKD through the stimulation of AGT, SGLT2, CD36, and FABP4 expression and lipid accumulation in RPTCs of T2D.

NADPH oxidase 4 facilitates progression of chondrosarcoma via generation of reactive oxygen species.

Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is an enzyme that regulates reactive oxygen species (ROS) generation, and its function in the development of chondrosarcoma remains unclear. In the present study, we studied NOX4 expression in chondrosarcoma by immunochemical examination, and analyzed the role of NOX4 in viability and apoptosis of human chondrosarcoma cell line SW1353 using NOX4 siRNA or NOX4 inhibitor GKT137831. NOX4 level significantly increased in tumor compared to that in para-carcinoma sample. The levels of NOX4 were positively correlated with histological grade and Musculoskeletal Tumor Society stage of the patients. NOX4 level was significantly increased in SW1353 compared with that in chondrocytes CHON-001. Knockdown of NOX4 or inhibition of NOX4 by GKT137831 both decreased generation of ROS, and induced growth inhibition and apoptosis in SW1353, accompanied with the activation of caspases (caspase-3, caspase-8 and caspses-9), upregulation of Bax, cytochrome C(cyt-c), cleaved-PARP and down-regulation of Bcl-2. Moreover, NOX4 siRNA and GKT137831 decreased the expression of p-Akt, p-ERK and p-p65 in SW1353 cells. In an in vivo study, NOX4 shRNA transfected SW1353 have shown impaired growth ability compared to the SW1353 when they were injected into the nude mice. Meanwhile, GKT137831 induced growth inhibition and apoptosis in SW1353 xenograft animals, together with increased expression of Bax, cyt-c, cleaved-PARP, and decreased expression of Bcl-2, p-Akt, p-ERK and p-p65. NOX4 plays a positive role in the development of chondrosarcoma and could serve as a promising target against chondrosarcoma clinically.

Targeting proteasomal deubiquitinases USP14 and UCHL5 with b-AP15 reduces 5-fluorouracil resistance in colorectal cancer cells.

5-Fluorouracil (5-FU) is the first-line treatment for colorectal cancer (CRC) patients, but the development of acquired resistance to 5-FU remains a big challenge. Deubiquitinases play a key role in the protein degradation pathway, which is involved in cancer development and chemotherapy resistance. In this study, we investigated the effects of targeted inhibition of the proteasomal deubiquitinases USP14 and UCHL5 on the development of CRC and resistance to 5-FU. By analyzing GEO datasets, we found that the mRNA expression levels of USP14 and UCHL5 in CRC tissues were significantly increased, and negatively correlated with the survival of CRC patients. Knockdown of both USP14 and UCHL5 led to increased 5-FU sensitivity in 5-FU-resistant CRC cell lines (RKO-R and HCT-15R), whereas overexpression of USP14 and UCHL5 in 5-FU-sensitive CRC cells decreased 5-FU sensitivity. B-AP15, a specific inhibitor of USP14 and UCHL5, (1-5 µM) dose-dependently inhibited the viability of RKO, RKO-R, HCT-15, and HCT-15R cells. Furthermore, treatment with b-AP15 reduced the malignant phenotype of CRC cells including cell proliferation and migration, and induced cell death in both 5-FU-sensitive and 5-FU-resistant CRC cells by impairing proteasome function and increasing reactive oxygen species (ROS) production. In addition, b-AP15 inhibited the activation of NF-κB pathway, suppressing cell proliferation. In 5-FU-sensitive and 5-FU-resistant CRC xenografts nude mice, administration of b-AP15 (8 mg·kg-1·d-1, intraperitoneal injection) effectively suppressed the growth of both types of tumors. These results demonstrate that USP14 and UCHL5 play an important role in the development of CRC and resistance to 5-FU. Targeting USP14 and UCHL5 with b-AP15 may represent a promising therapeutic strategy for the treatment of CRC.

Membranous nephropathy: Mechanistic insights and therapeutic perspectives.

Membranous nephropathy (MN) is one of the most common causes of non-diabetic nephrotic syndrome in adults. About 80% of cases are renal limited (primary MN) and 20% are associated with other systemic diseases or exposures (secondary MN). Autoimmune reaction is the main pathogenic factor of MN, and the discovery of autoantigens including the phospholipase A2 receptor and thrombospondin type-1 domain-containing protein 7A has led to new insights into the pathogenesis, they can induce humoral immune responses led by IgG4 makes them suitable for the diagnosis and monitoring of MN. In addition, complement activation, genetic susceptibility genes and environmental pollution are also involved in MN immune response. In clinical practice, due to the spontaneous remission of MN, the combination of supportive therapy and pharmacological treatment is widely used. Immunosuppressive drugs are the cornerstone of MN treatment, and the dangers and benefits of this approach vary from person to person. In summary, this review provides a more comprehensive review of the immune pathogenesis, interventions and unresolved issues of MN in the hope of providing some new ideas for clinical and scientific researchers in the treatment of MN.

Circularly polarized luminescence and magneto-optic effects from chiral Dy(III) single molecule magnets.

A new pair of multifunctional Zn(II)-Dy(III) enantiomers based on the chiral Schiff-base ligands [R,R-ZnLDy(H2O)(NO3)3] (1R2R-ZnDy) and [S,S-ZnLDy(H2O)(NO3)3] (1S2S-ZnDy) (H2L = phenol, 2,2'-[[(1R,2R/1S,2S)-1,2-diphenyl-1,2-ethanediyl]bis[(E)-nitrilomethylidyne]]bis[6-methoxy]) was synthesized and characterized. Magnetic studies indicate that 1R2R-ZnDy behaves as a single-molecule magnet. Enantiomers 1R2R-ZnDy and 1S2S-ZnDy show chiroptical activity and circularly polarized luminescence in the N,N-dimethylformamide (DMF) solution. The chiral Zn(II)-Dy(III) complexes display magnetic circular dichroism signals at room temperature. Accordingly, these complexes will inspire intriguing research on single-molecule magnets with circular polarization of luminescence activity and magneto-optic effects, which will give new clues to design multifunctional molecular magnetic materials.

Moshen granule ameliorates membranous nephropathy by blocking intrarenal renin-angiotensin system signalling via the Wnt1/ß-catenin pathway.

BACKGROUND: Membranous nephropathy (MN) is one of the cardinal causes of nephrotic syndrome in adults, but an adequate treatment regimen is lacking. PURPOSE: We assessed the effect of Moshen granule (MSG) on patients with MN and cationic bovine serum albumin (CBSA)-induced rats. We further identified the bioactive components of MSG and revealed the underlying molecular mechanism of its renoprotective effects. METHODS: We determined the effect of MSG on patients with MN and CBSA-induced rats and its components on podocyte injury in zymosan-activated serum (ZAS)-elicited podocytes and revealed their regulatory mechanism on the Wnt/ß-catenin/renin-angiotensin system (RAS) signalling axis. RESULTS: MSG treatment improved renal function and reduced proteinuria in MN patients and significantly reduced proteinuria and preserved the protein expression of podocin, nephrin, podocalyxin and synaptopodin in CBSA-induced MN rats. Mechanistically, MSG treatment significantly inhibited the protein expression of angiotensinogen, angiotensin converting enzyme and angiotensin II type 1 receptor, which was accompanied by inhibition of the protein expression of Wnt1 and ß-catenin and its downstream gene products, including Snail1, Twist, matrix metalloproteinase-7, plasminogen activator inhibitor-1 and fibroblast-specific protein 1, in CBSA-induced MN rats. We further identified 81 compounds, including astragaloside IV (AGS), calycosin, barleriside A and geniposidic acid, that preserve the podocyte-specific protein expression in ZAS-induced podocytes. Among these four compounds, AGS exhibited the strongest inhibitory effects on podocyte protein expression. AGS treatment significantly inhibited the protein expression of RAS components and Wnt1 and ß-catenin and its downstream gene products in ZAS-induced podocytes. In contrast, the inhibitory effect of AGS on podocyte-specific proteins, ß-catenin downstream gene products and RAS components was partially abolished in ZAS-induced podocytes treated with ICG-001 and ß-catenin siRNA. CONCLUSION: This study first demonstrates that AGS mitigates podocyte injury by inhibiting the activation of RAS signalling via the Wnt1/ß-catenin pathway by both pharmacological and genetic methods. Therefore, AGS might be considered a new ß-catenin inhibitor that inhibits the Wnt1/ß-catenin pathway to retard MN in patients.

Deciphering the role of lipoproteins and lipid metabolic alterations in ageing and ageing-associated renal fibrosis.

Fibrosis is the ultimate pathological feature of many chronic diseases, and ageing a major risk factor for fibrotic diseases. Current therapies are limited to those that reduce the rate of functional decline in patients with mild to moderate disease, but few interventions are available to specifically target the pathogenesis of fibrosis. In this context, new treatments that can significantly improve survival time and quality of life for these patients are urgently needed. In this review, we outline both the synthesis and metabolism of lipids and lipoproteins associated with ageing-associated renal fibrosis and the prominent contribution of lipids and lipidomics in the discovery of biomarkers that can be used for the prevention, diagnosis, and treatment of renal ageing and fibrosis. Next, we describe the effect of dyslipidaemia on ageing-related renal fibrosis and the pathophysiological changes in the kidney caused by dyslipidaemia. We then summarize the enzymes, transporters, transcription factors, and RNAs that contribute to dysregulated lipid metabolism in renal fibrosis and discuss their role in renal fibrosis in detail. We conclude by discussing the progress in research on small molecule therapeutic agents that prevent and treat ageing and ageing-associated renal fibrosis by modulating lipid metabolism. A growing number of studies suggest that restoring aberrant lipid metabolism may be a novel and promising therapeutic strategy to combat ageing and ageing-associated renal fibrosis.

Transforming growth factor-ß signaling: From tissue fibrosis to therapeutic opportunities.

Fibrosis refers to the excessive deposition of extracellular matrix components in the processes of wound repair or tissue regeneration after tissue damage. Fibrosis occurs in various organs such as lung, heart, liver, and kidney tissues, resulting in the failure of organ structural integrity and its functional impairment. It has long been thought to be relentlessly progressive and irreversible process, but both preclinical models and clinical trials in multiorgans have shown that fibrosis is a highly dynamic process. Transforming growth factor-beta (TGF-ß) is a superfamily of related growth factors. Many studies have described that activation of profibrotic TGF-ß signaling promotes infiltration and/or proliferation of preexisting fibroblasts, generation of myofibroblasts, extracellular matrix deposition, and inhibition of collagenolysis, which leads to fibrosis in the pathological milieu. This review describes the effect of TGF-ß signaling in fibrotic-associate lung, heart, liver, and kidney tissues, followed by a detailed discussion of canonical and non-canonical TGF-ß signaling pathway. In addition, this review also discusses therapeutic options by using natural products and chemical agents, for targeting tissue fibrosis via modulating TGF-ß signaling to provide a more specific concept-driven therapy strategy for multiorgan fibrosis.

Imaging evaluation of cerebrospinal fluid otorrhea associated with inner ear malformation in children / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the imaging evaluation of cerebrospinal fluid (CSF) otorrhea associated with inner ear malformation (IEM) in children. Methods: The clinical data of 28 children with CSF otorrhea associated with IEM confirmed by surgical exploration in Beijing Children's Hospital, from Nov, 2016 to Jan, 2021, were analyzed retrospectively,including 16 boys and 12 girls, aged from 8-month to 15-year and 8-month old, with a median age of 4-year old. The shapes of stapes were observed during the exploration surgery, and the imaging features of temporal bone high resolution CT(HRCT) and inner ear MRI pre- and post-operation were analyzed. Results: In 28 children with CSF otorrhea, 89.3%(25/28) had stapes footplates defect during exploration. Preoperative CT showed indirect signs such as IEM, tympanic membrane bulging, soft tissue in the tympanum and mastoid cavity. IEM included four kinds: incomplete partition type I (IP-Ⅰ), common cavity (CC), incomplete partition type Ⅱ (IP-Ⅱ), and cochlear aplasia (CA); 100%(28/28) presented with vestibule dilation; 85.7%(24/28) with a defect in the lamina cribrosa of the internal auditory canal. The direct diagnostic sign of CSF otorrrhea could be seen in 73.9%(17/23) pre-operative MRI: two T2-weighted hyperintense signals between vestibule and middle ear cavity were connected by slightly lower or mixed intense T2-weighted signals, and obvious in the coronal-plane; 100%(23/23) hyperintense T2-weighted signals in the tympanum connected with those in the Eustachian tube.In post-operative CT, the soft tissues in the tympanum and mastoid cavity decreased or disappeared as early as one week. In post-operative MRI, the hyperintense T2-weighted signals of tympanum and mastoid decreased or disappeared in 3 days to 1 month,soft tissues tamponade with moderate intense T2-weighted signal were seen in the vestibule in 1-4 months. Conclusions: IP-Ⅰ, CC, IP-Ⅱ and CA with dilated vestibule can lead to CSF otorrhea. Combined with special medical history, T2-weighted signal of inner ear MRI can provide diagnostic basie for most children with IEM and CSF otorrhea.HRCT and MRI of inner ear can also be used to evaluate the effect of surgery.

Clinical features of children with coronavirus disease 2019 in different age groups during the epidemic of Omicron variant / 中国当代儿科杂志

OBJECTIVES@#To study the differences in the clinical features of children with coronavirus disease 2019 (COVID-19) in different age groups during the epidemic of Omicron variant.@*METHODS@#A retrospective analysis was performed on the clinical data of 211 children with COVID-19 who were admitted to the Department of General Pediatrics, Zhongshan People's Hospital, from December 9, 2022 to January 8, 2023. According to their age, they were divided into 4 groups: 1 month-<1 year (n=84), 1-<3 years group (n=64), 3-<5 years (n=29), and ≥5 years (n=34). The above groups were compared in terms of general status, clinical features, ancillary examination results, treatment, and outcome.@*RESULTS@#The children aged <3 years accounted for 70.1% (148/211) of all hospitalized children with COVID-19, and the 3-<5 years group and the ≥5 years group had a significantly higher proportion of children with underlying diseases than the 1 month-<1 year group and the 1-<3 years group (P<0.05). Compared with the other three groups, the 1 month-<1 year group had significantly higher incidence rates of dyspnea, nasal congestion/nasal discharge, diarrhea and significantly lower incidence rates of convulsion and nervous system involvement (P<0.05). Moreover, compared with the other three groups, the 1 month-<1 year group had significantly higher incidence rates of increases in bile acid and creatine kinase isoenzyme and significantly lower incidence rates of decreased platelet count, increased neutrophil percentage, and decreased lymphocyte percentage (P<0.05). The 1 month-<1 year group had a significantly higher incidence rate of mild COVID-19 than the 1-<3 years group and a significantly lower incidence rate of severe/critical COVID-19 than the other three groups (P<0.05). Compared with the other three groups, the 1 month-<1 year group had a significantly higher proportion of children receiving oxygen inhalation therapy (P<0.05).@*CONCLUSIONS@#Children with COVID-19 in different age groups have different clinical features during the epidemic of Omicron variant, especially between the children aged 1 month to <1 year and those aged ≥1 year.

The influence of COVID-19 infection on treatments of patients with acute type A aortic dissection / 中华胸心血管外科杂志

Objective:To investigate the differences in outcomes of surgical strategies and prognosis of patients with acute type A aortic dissection(ATAAD) during the period of COVID-19 Omicron variant epidemic compared with the non-epidemic period.Methods:Clinical data were retrospectively collected from ATAAD patients during the COVID-19 Omicron variant epidemic(December 7, 2022 to January 10, 2023) and during the non-epidemic period(December 7, 2019 to January 10, 2020) to compare the differences in surgical strategies, perioperative mortality, and perioperative complication rates in ATAAD patients during the two different periods.Results:There were 14 patients in the COVID-19 infected group and 43 patients in the control group. Patients in the infected group had a shorter mean aortic clamp time[(89.71±16.27)min vs.(110.09±28.99)min, P<0.01], a significantly higher postoperative mortality rate relative to the control group(21.43% vs. 2.33%, P=0.02), a significantly longer length of stay in the ICU(3 days vs. 2 days, P=0.04) and the duration of intubation time(34 h vs. 14 h, P<0.01), and the incidence of adverse events, mainly cerebral infarction, was higher in infected group(28.57% vs. 6.98%, P=0.03). Conclusion:During the COVID-19 Omicron variant strain epidemic, our center preferred a more conservative surgical strategy in COVID-19 infected patients. Although the COVID-19 infection increased the postoperative mortality and complication rate of ATAAD, patients still achieve a more satisfactory outcome. Therefore, surgical treatment should be timely performed for ATAAD patients.

Midterm clinical results of Sun's procedure with median resternotomy / 中华胸心血管外科杂志

Objective:To summarize the clinical data of Sun's procedure(total aortic arch replacement with frozen elephant trunk technique) in the treatment of complex aortic arch disease after previous cardiac surgery.Methods:From January 1, 2018 to December 31, 2020, a total of 55 patients underwent resternotomy Sun's procedure in the Aortic Surgery Center of Beijing Anzhen Hospital, including 41 males and 14 females, with a mean age of(45.4±12.7) years old, were retrospectively analyzed. The indications of primary cardiac surgery included type A aortic dissection, aortic root or ascending aortic aneurysm, heart valve surgery, and coronary heart disease. Indications for reoperation included residual aortic dissection larger than 55 mm in diameter, aortic aneurysm dilation, new type A aortic dissection, anastomotic leakage with symptoms, and pseudoaneurysm. All the operations were performed under general anesthesia and median resternotomy, total aortic arch replacement with the stented elephant trunk implantation and were performed by anterograde unilateral or bilateral cerebral perfusion.Results:There was no intraoperative death, and the postoperative mortality was 9.1%(5/55). The causes of death were 2 cases of low cardiac output, 1 case of respiratory failure, 1 case of cerebral complications, and 1 case of gastrointestinal bleeding. Except death, there were 2 cases of postoperative cerebral complications(2/50, 4%), 5 cases of spinal cord injury(transient paraplegia)(5/50, 10%), the median duration of ventilator use was 17 hours(14-42 h). Other postoperative complications included respiratory insufficiency requiring ventilatory support longer than 48 hours(8/50, 16%), renal insufficiency requiring temporary dialysis(2/50, 4%). The follow-up time was(25.9±11.2) months(10-47 months), during which 1 case died due to cerebral complication, 4 cases underwent total thoracoabdominal aorta replacement, and 1 case underwent anastomotic leakage repair.Conclusion:It is safe and effec to perform Sun's procedure(total aortic arch replacement with frozen elephant trunk technique) in the treatment of complex arch disease after previous cardiac surgery.

The role of SUMOylation in the protective mechanisms of therapeutic hypothermia on neonatal hypoxic-ischemic encephalopathy / 中国新生儿科杂志

Objective:To study the role of SUMOylation in the process of therapeutic hypothermia on neural stem cells (NSCs) in neonatal hypoxic-ischemic encephalopathy.Methods:SUMOylation is an essential post-translational modification involving small ubiquitin-like modifiers (SUMOs). Primary-cultured NSCs from mice were assigned into four groups: control group, hypoxia group, hypothermia group and hypoxia+hypothermia group. Western Blot was used to detect the protein levels of SUMO2/3, hypoxia-inducible factor-1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator factor 1α (PGC-1α) and octamer binding transcription factor 4 (Oct4). The diameters of NSCs were compared. ELISA was used to detect lactate dehydrogenase (LDH) level. Apoptosis was examined using flow cytometry. Immunofluorescence method was used to measure the differentiation of NSCs into neuronal cells.Results:Compared with the control group, the levels of SUMO2/3, HIF-1αand PGC-1α in NSCs of the hypoxia group increased 33%, 126% and 140%, respectively ( P<0.05). Compared with the control group, the levels of SUMO2/3 and PGC-1α in NSCs of the hypothermia group increased 52% and 536%, respectively ( P<0.05). Compared with the hypoxia group, the levels of SUMO2/3, HIF-1α, PGC-1α and Oct4 in the hypoxia+hypothermia group increased 44%, 40%, 230% and 59%, respectively ( P<0.05). The diameters of NSCs in hypoxia group, hypothermia group and hypoxia+hypothermia group were smaller than control group, and hypoxia+hypothermia group smaller than hypoxia group ( P<0.05). No significant differences existed in LDH levels between hypothermia group and control group ( P>0.05). LDH level in hypoxia+hypothermia group were significantly lower than hypoxia group ( P<0.05). No significant differences existed in the cell death rates between hypothermia group and control group ( P>0.05). The cell death rate in hypoxia+hypothermia group was significantly lower than hypoxia group ( P<0.05). Compared with the control group, the expressions of Nestin in both hypoxia group and hypothermia group were increased, but neuron specific enolase (NSE) were decreased ( P<0.05). Compared with hypoxia group and hypothermia group, the level of Nestin in hypoxia+hypothermia group was further increased, while NSE was further decreased ( P<0.05). Conclusions:Therapeutic hypothermia may increase the tolerance of NSCs to hypoxia by enhancing SUMO modification of proteins, providing theoretical basis for the treatment of hypoxic-ischemic encephalopathy with therapeutic hypothermia.

Effects of individualized parenteral nutrition versus pre-mixed parenteral nutrition on liver function of patients with acute kidney injury / 中国药房

OBJECTIVE To compare the effects of individualized parenteral nutrition versus pre-mixed parenteral nutrition on liver function of patients with acute kidney injury （AKI）. METHODS Totally 97 AKI patients in the intensive care unit of our hospital from January 2021 to March 2022 were collected and randomly divided into pre-mixed multi-chamber bag （MCB） group （48 cases） and compounded parenteral nutrition （COM） group （49 cases）. The patients in both groups were given routine treatment to correct the reversible cause in time， and parenteral nutrition support treatment was started within 48 hours after the fluid resuscitation was successful or the hemodynamics of low-dose vasoactive drugs were stable. MCB group was given one bag of Fat emulsion amino acid （17） glucose （11%） injection， intravenous infusion， once a day； COM group was given Medium/long chain Fat emulsion injection （C8-24Ve） 0.5-0.8 g/kg+Compound amino acid 18AA-Ⅶ 1.0-1.2 g/kg+Glucose injection 1.5-2.5 g/kg+one Water soluble vitamin injection+Fat-soluble vitamin injection （Ⅱ） 10 mL+Multiple trace element injection （Ⅱ） 10 mL+ individualized supplement of sodium chloride and potassium chloride， with a ratio of glucose to lipid of 5∶5 and a ratio of heat to nitrogen of 100∶1. The treatment course of both groups lasted for 7 days. The percentage of abnormal liver function， the levels of liver function indexes [alanine aminotransferase （ALT）， total bilirubin （TBIL）， aspartate transaminase （AST）]， albumin （ALB）， interleukin-6 （IL-6） and C-reactive protein （CRP） were observed in 2 groups before and after treatment. RESULTS After treatment， the ratio of liver dysfunction， the levels of ALT， AST and CRP in MCB group were significantly higher than before treatment； the ratio of liver dysfunction， the levels of ALT and CRP in MCB group were significantly higher than COM group （P＜0.05）. There were no statistical significance in the ratio of liver dysfunction， the levels of ALT， AST， TBIL and CRP in COM group before and after treatment （P＞0.05）. CONCLUSIONS Individualized parenteral nutrition support treatment can reduce the occurrence of liver injury and improve the nutritional status of AKI patients.