[Clinical characteristics and prognosis in 12 children with SARS-CoV-2 Omicron variant infection-associated acute necrotizing encephalopathy]. / 12ä¾‹æ–°åž‹å† çŠ¶ç— æ¯’Omicronå˜å¼‚æ ªæ„ŸæŸ“ç›¸å ³æ€¥æ€§åæ­»æ€§è„‘ç— å„¿ç«¥çš„ä¸´åºŠç‰¹ç‚¹åŠé¢„åŽåˆ†æž.

OBJECTIVES: To study the clinical characteristics and prognosis of SARS-CoV-2 Omicron variant infection-associated acute necrotizing encephalopathy (ANE) in children. METHODS: A retrospective analysis was conducted on the medical data of 12 children with SARS-CoV-2 Omicron variant infection-associated ANE who were admitted to the Pediatric Intensive Care Unit, Qingdao Women and Children's Hospital from December 18 to 29, 2022. The children were divided into two groups based on outcomes: death group (7 cases) and survival group (5 cases). The clinical manifestations and auxiliary examination results were compared between the two groups. RESULTS: The median age of the 12 patients was 30 months, with a male-to-female ratio of 1:1. All patients presented with persistent high fever, with a median highest body temperature of 41℃. The median time from fever onset to seizure or consciousness disturbance was 18 hours. The death group had a higher proportion of neurogenic shock, coagulation dysfunction, as well as elevated lactate, D-dimer, interleukin-6, interleukin--8, and interleukin-10 levels compared to the survival group (P<0.05). CONCLUSIONS: Children with SARS-CoV-2 Omicron variant infection-associated with ANE commonly present with persistent high fever, rapidly progressing disease, and have a high likelihood of developing consciousness disorders and multiorgan dysfunction within a short period. The occurrence of neurogenic shock, coagulation dysfunction, and significantly elevated cytokine levels suggests an increased risk of mortality.

CircRNA_100565 contributes to cisplatin resistance of NSCLC cells by regulating proliferation, apoptosis and autophagy via miR-337-3p/ADAM28 axis.

Circular RNAs (circRNAs) have been revealed to involve in the chemoresistance of various cancers, including non-small cell lung cancer (NSCLC). Here, we further investigate the role of circRNA_100565 in NSCLC cisplatin (DDP) resistance. The expression of circRNA_100565 and microRNA (miR)-337-3p, and ADAM metallopeptidase domain 28 (ADAM28) mRNA was detected using quantitative real-time polymerase chain reaction. Cell viability and apoptosis were measured by cell counting kit-8 assay and flow cytometry, respectively. Western blot was used to detect the level of ADAM28 and autophagy-related protein. The interaction between miR-337-3p and circRNA_100565 or ADAM28 was confirmed by dual-luciferase reporter assay or pull-down assay. In vivo experiments were conducted via the murine xenograft model. We found CircRNA_100565 was up-regulated in NSCLC DDP-resistant tissues and cell lines, and its high expression was associated with shorter overall survival of NSCLC patients. CircRNA_100565 deletion mitigated DDP resistance, reflected by the suppression of proliferation and autophagy, the reduction of IC50 value, as well as enhancement of apoptosis in DDP-resistant NSCLC cells. MiR-377-3p was confirmed to directly bind to circRNA_100565 or ADAM28 3'-UTR. Moreover, circRNA_100565 indirectly regulated ADAM28 expression by sponging miR-377-3p in NSCLC cells. Additionally, circRNA_100565 deletion-induced sensitivity of NSCLC resistant cells to DDP could be remarkably attenuated by miR-377-3p inhibition or ADAM28 re-expression. Meanwhile, circRNA_100565 knockdown contributed to the anti-tumor effects of DDP on NSCLC in vivo.CONCLUSION: CircRNA_100565 was an independent prognostic factor for NSCLC patient survival, and enhanced the resistance of NSCLC cells to cisplatin by regulating cell proliferation, apoptosis and autophagy via miR-337-3p/ADAM28 axis, shedding light on the development of a novel therapeutic strategy to boost the effectiveness of NSCLC chemotherapy.

Retrospective Analysis of Clinical Outcomes in Patients with Immunoglobulin A Nephropathy and Persistent Hematuria Following Renin-Angiotensin System Blockade.

BACKGROUND Recent guidelines recommend that patients with immunoglobulin A nephropathy (IgAN) and proteinuria 0.5-1 g/d and >1 g/d be treated with long-term renin-angiotensin system blockade (RASB). This study investigated whether patients with IgAN and persistent hematuria, but without proteinuria, can benefit from RASB. MATERIAL AND METHODS IgAN patients with persistent hematuria at four centers were recruited from January 2013 to December 2018. Patients were divided into those who did and did not receive long-term RASB. The primary outcome was the appearance of proteinuria, and the secondary outcomes were the decreased percentage of hematuria, rate of decline in estimated glomerular filtration rate (eGFR) and final blood pressure. The effects of RASB on these outcomes were assessed by multivariate Cox regression models and propensity score matching. RESULTS Of the 110 eligible patients, 44 (40.0%) received RASB and 66 (60.0%) did not. Treated patients had higher diastolic pressure. The unadjusted primary outcome, the appearance of proteinuria, was significantly less frequent in individuals who were than who were not treated with RASB. Multivariate Cox regression showed that RASB reduced the risk of the primary outcome and the levels of hematuria. The rate of eGFR decline and final blood pressure did not differ in the two groups. CONCLUSIONS RASB reduced the risk of proteinuria development and increased the remission of hematuria in patients with IgAN who presented with persistent hematuria alone. RASB, however, did not affect blood pressure in patients without hypertension and did not affect the rate of eGFR decline.

Ultrasound guided continuous Quadratus Lumborum block hastened recovery in patients undergoing open liver resection: a randomized controlled, open-label trial.

BACKGROUND: Quadratus lumborum (QL) block is increasingly being used as a new abdominal nerve block technique. In some studies of mid and lower abdominal and hip analgesia, continuous QL block achieved favorable outcomes as an alternative to continuous intravenous analgesia with opioids. However, the use of continuous QL block for upper abdominal pain is less well characterized. This study aimed to investigate the effects of continuous anterior QL block (CQLB) on postoperative pain and recovery in patients undergoing open liver resection. METHODS: Sixty-three patients underwent elective open liver resection were randomly divided into continuous anterior QL block (CQLB, n = 32) group and patient-controlled intravenous analgesia (PCIA, n = 31) group. Patients in CQLB group underwent ultrasound-guided anterior QL block at the second lumbar vertebral transverse processes before general anesthesia, followed by postoperative CQLB analgesia. Patients in PCIA group underwent continuous intravenous analgesia postoperatively. Postoperative numerical rating scale (NRS) pain scores upon coughing and at rest, self-administered analgesic counts, rate of rescue analgesic use, time to first out-of-bed activity and anal flatus after surgery, and incidences of analgesic-related adverse effects were recorded. RESULTS: Postoperative NRS pain scores on coughing in CQLB group at different time points and NRS pain score at rest 48 h after surgery were significantly lower than those in PCIA group (P < 0.05). Time to first out-of-bed activity and anal flatus after surgery in CQLB group were significantly earlier than those in PCIA group (P < 0.05). No significant differences of postoperative self-administered analgesic counts, rate of postoperative rescue analgesic usage, or incidences of analgesic-related adverse effects were found between the two groups (P > 0.05). CONCLUSIONS: Ultrasound-guided anterior QL block significantly alleviated the pain during coughing after surgery, shortened the time to first out-of-bed activity and anal flatus, promoting postoperative recovery of the patients undergoing open liver resection. TRIAL REGISTRATION: This study has been registered in April 1, 2018 on Chinese Clinical Trail Registry, the registration number is ChiCTR1800015454 .

Intravenous anesthetic ketamine attenuates complete Freund's adjuvant-induced arthritis in rats via modulation of MAPKs/NF-κB.

BACKGROUND: The current study was intended to investigate the effect of ketamine (KET) on complete Freund's adjuvant (CFA)-induced arthritis in rats. METHODS: The CFA was administered in the hind paw of the rats for the induction of adjuvant-induced arthritis. The paw swelling of experimental animals was measured as hind paw volume. Hematoxylin and eosin staining was estimated and pathological changes in the joint tissues were observed under a light microscope. Furthermore, the bicinchoninic acid assay was used for protein quantification. The antibody-reactive bands were visualized using enhanced chemiluminescence. RESULTS: The present study showed that KET significantly reduces the severity of arthritis in CFA mice. The therapeutic effects were linked with reduced joint swelling and destruction, as evidenced by analyzing rat paws. The KET also revealed to attenuate the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6). In western blot analysis, KET inhibit phosphorylation of MAPKs, IκBα and nuclear translocation NF-κB in the inflammatory joints of AIA rats. Moreover, KET showed to induce apoptosis via mitochondrial signalling pathways (Bcl2, Bax, cytochrome C, cleaved caspase-3 and cleaved caapse-9). CONCLUSION: Taken together, KET show significant anti-rheumatoid arthritis activity via multiple mechanisms and may thus have therapeutic benefits for RA.

Exome Sequencing Identifies a Novel DES Mutation (R227C) in a Chinese Dilated Cardiomyopathy Family.

OBJECTIVES: Dilated cardiomyopathy (DCM) is a common disease in the clinic, and it is the leading cause of heart failure and sudden cardiac death. Previous studies have proven that genetic factors play a crucial role in the occurrence of DCM; more than 50 disease genes including desmin (DES) have been identified to be associated with DCM. At present, most DES mutations are reported in desmin-related myofibrilla myopathy patients, but variants leading to isolated DCM are rarely reported. METHODS: We applied whole-exome sequencing and cardiomyopathy-related gene filtering strategies to discover the genetic factors in a Chinese DCM family. RESULTS: A novel mutation (c.679 C>T /p.R227C) in exon 3 of DES was identified and cosegregated with the affected members of a Chinese family with isolated DCM phenotypes (left ventricle and left atrial diameters). CONCLUSION: This mutation leads to a substitution of arginine by cysteine and it is predicted to be deleterious by bioinformatics programs. Our study not only contributes to the genetic diagnosis and counseling of families with DCM, but it also further proves that DES mutations may lead to isolated DCM and provides a new case for the study of the relationship between DES mutations and DCM.

[Effect of dexmedetomidine hydrochloride on H2O2-induced oxidative stress and inflammatory response in Kupffer cells].

OBJECTIVE: To evaluate whether dexmedetomidine hydrochloride, an α(2)-adrenergic receptor agonist, can prevent H(2)O(2)-induced oxidative stress and inflammatory response in Kupffer cells.
 METHODS: H(2)O(2)-induced oxidative damage model of Kupffer cell was established. Kupffer cells were pre-conditioned by dexmedetomidine hydrochloride or Yohimbine for 24 h. MTT colorimetry was used to demonstrate the survival rate of Kupffer cells. The levels of lactate dehydrogenase (LDH), malonaldehyde (MDA) and TNF-α in the culture medium were assessed by corresponding kits.
 RESULTS: Dexmedetomidine hydrochloride protected Kupffer cells from H(2)O(2)-induced oxidative damage, showing an increase in the cell survival rate while a decrease in LDH, MDA and TNF-α release in the culture supernatant. Yohimbine, an α(2)-adrenergic receptor antagonist, completely neutralized the protective effect of Dexmedetomidine hydrochloride on Kupffer cells. Yohimbine itself had no effect on H(2)O(2)-induced oxidative damage and inflammatory response.
 CONCLUSION: Dexmedetomidine hydrochloride can prevent H(2)O(2)-induced oxidative stress and inflammatory response in Kupffer cells through activation of α(2)-adrenergic receptors.

Effect of dexmedetomidine on lung ischemia­reperfusion injury.

Dexmedetomidine, a specific selective α2-adrenergic agonist, does not only have the characteristics of being a sedative and analgesic, but also exhibits a protective role in brain ischemia-reperfusion injury and inhibits the inflammation in animals with sepsis. The objective of the present study was to investigate whether dexmedetomidine is capable of attenuating rat pulmonary damage induced by ischemia-reperfusion injury, which is a type of acute sterile lung injury. Sprague-Dawley rats were randomly assigned into six groups: The sham-operated (sham) group, the lung ischemia-reperfusion (I/R) group, intravenous injection of dexmedetomidine 2.5 µg/kg/h (Dex2.5) or 5 µg/kg/h (Dex5) for 1 h prior to ischemia, combination of α2-adrenergic antagonist yohimbine prior to dexmedetomidine pre-treatment (Dex+Yoh) and pre-administration of yohimbine alone (Yoh) prior to ischemia. Lung injury was assessed by the histopathological changes, arterial blood gas, wet/dry (w/d) weight ratio and myeloperoxidase (MPO) activity of the lung. The concentration of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) in bronchoalveolar lavage fluid (BALF) was measured by an enzyme-linked immunosorbent assay. The expression of toll-like receptor-4 (TLR4) and myeloid differentiation factor 88 (MyD88) mRNA in the lung were determined by quantitative PCR, and phosphorylated levels of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK)1/2 were determined by western blotting. Pre-treatment with dexmedetomidine significantly reduced the lung injury, w/d weight ratio and MPO activity, and decreased the concentration of TNF-α, IL-6 and MCP-1 in BALF compared with the I/R group. The expression of TLR4 and MyD88 mRNA and the levels of phosphorylated JNK and ERK1/2 in the lung tissue were markedly downregulated by intravenous injection of dexmedetomidne for 1 h prior to lung I/R. The protective effects of dexmedetomidine on the lung were not completely reversed by the α2-adrenergic antagonist, yohimbine. Pre-treatment with dexmedetomidine is capable of reducing pulmonary damage and inhibiting sterile inflammation induced by lung I/R injury. TLR4/MyD88/mitogen-activated protein kinase (MAPK) signaling is involved in the protective mechanism of dexmedetomidine through α2-adrenoceptor independence.

Effect of dexmedetomidine pretreatment on lung injury following intestinal ischemia-reperfusion.

Reperfusion injury is tissue damage caused by the re-supply of blood following a period of ischemia in tissues. Intestinal ischemia-reperfusion injury (IRI) is an extremely common clinical event associated with distant organ injury. The intestine serves as the initial organ of multi-system organ dysfunction syndrome. It is extremely important to identify a method to protect against IRI, as it is a key factor associated with morbidity and mortality in patients. In the present study, the protective effects of pretreatment with dexmedetomidine hydrochloride were investigated. Rats were divided into six groups and models of intestinal ischemia were created in the five groups. Certain groups were pretreated with dexmedetomidine hydrochloride. The levels of TNF-α and IL-6 were measured by enzyme-linked immunosorbent assay in order to evaluate the injury. Tissue sections were stained with hematoxylin and eosin to visualize the damage. qPCR and western blotting were performed to examine the inflammatory status. Pretreatment with various doses of dexmedetomidine hydrochloride significantly reduced the pathological scores and the inflammatory reaction. The levels of TNF-α, IL-6, TLR4 and MyD88 were decreased in the dexmedetomidine hydrochloride treatment groups compared with those in the sham control and untreated ischemia reperfusion groups. The results of the present study indicate that pretreatment with dexmedetomidine hydrochloride may be a useful method of reducing the damage caused by IRI.

[Effect of dexmedetomidine hydrochloride on H2O2-induced oxidative stress in alveolar macrophages].

OBJECTIVE: To evaluate whether dexmedetomidine hydrochloride, an α2-adrenergic receptor agonist, can prevent oxidative damage to alveolar macrophages induced by H2O2. METHODS: We used methyl thiazolyl tetrazolium (MTT) colorimetry to test the effect of different concentrations and action time of H2O2 on the survival rate of alveolar macrophages, and then we chose the appropriate H2O2 concentration and action time to build NR8383 cell oxidative damage model. After pre-conditioning of 0.01, 0.10, and 1.00 µmol/L dexmedetomidine hydrochloride for 24 hours, MTT colorimetry was used to demonstrate the survival rate of NR8383 cells damaged by H2O2, and the release of lactate dehydrogenase (LDH) and TNF-α by H2O2-damaged NR8383 cells was detected by corresponding kit. RESULTS: At 50-300 µmol/L, H2O2 caused concentration-dependent oxidative damage in the alveolar macrophages, decreased the cell survival rate, and increased LDH and TNF-α release. At 0.01-1.00 µmol/L dexmedetomidine hydrochloride concentration-dependently protected NR8383 cells from oxidative damage induced by H2O2, significantly increased the cell survival rate, decreased LDH and TNF-α release, and this effect of dexmedetomidine hydrochloride was dose-dependent. Yohimbine, an α2 - adrenergic receptor antagonist, completely neutralized the protective effect of dexmedetomidine hydrochloride on NR8383 cells without affecting the oxidative damage of NR8383 cells. CONCLUSION: Dexmedetomidine hydrochloride can prevent alveolar macrophages from oxidative damage induced by H2O2, which may play a protective role through α2 - adrenergic receptors.

[Effects of different doses of fentanyl on the stress response in patients undergoing valve replacement].

OBJECTIVE: To investigate the effects of different doses of fentanyl on the stress response in valve replacement surgery during cardiopulmonary bypass (CPB). METHODS: Thirty ASA II-III adult patients scheduled for cardial valve replacement were randomly divided into 3 groups: Group A (fentanyl 30 microg/kg), Group B (fentanyl 60 microg/kg), and Group C (fentanyl 100 microg/kg). Anesthesia was induced with medazalam 0.1 mg/kg, fentanyl 10 microg/kg and vecuronium 0.1 mg/kg; And were maintained with fentanyl and propofol infusion. Remained dose of fentanyl was used before the CPB. MAP, CVP, HR, P(ET)CO2, SpO2, nasal and rectal temperature were monitored continuously. Blood samples were taken before the operation (T1), before the CPB (T2), 30 min after the aortic declamping (T3), 2 h after the aortic declamping (T4), 24 h (T5) after the operation to determine the plasma levels of glucose, adrenocorticotropic hormone (ACTH), angiotensin II (AT II) and cortisol. RESULTS: Levels of glucose, ACTH, AT II and cortisol after the CPB (T3, T4 and T5) in 3 groups were significantly increased compared with that of T1 (P < 0.05 or P < 0.01). After CPB, at the same time point, among the 3 groups, the levels of the above index of Group A were the most highest, that of Group C were the most lowest. Glucose, ACTH, AT II and cortisol levels at T3 and T4 were significantly lower in Group B and C than those in Group A ( P < 0.05); But there was no significant difference between Group B and C. The duration of stay in the ICU and time of endotracheal extubation were significantly longer in patients of Group C than Group A and B (P < 0.05). CONCLUSION: Fentanyl (30-100 microg/kg) can completely suppress the stress response induced by intubation and intense surgical stimulus before CPB. Different doses of fentanyl seemed to be effective in reducing CPB-induced stress response. But the effect was not dependent on dose. So 60 microg/kg fentanyl seemed to be an ideal dose.

[Effects of fentanyl on cytokines and MDA during cardiopulmonary bypass in patients undergoing valve replacement].

OBJECTIVE: To investigate the effect of fentanyl on cytokines and MDA in valve replacement surgery during cardiopulmonary bypass ( CPB). METHODS: Thirty ASA II approximately III adult patients scheduled for cardial valve replacement were randomly divided into 3 groups: Group A (fentanyl 30 microg/ kg), Group B (fentanyl 60 microg/kg), and Group C (fentanyl 100 microg/kg). Anesthesia was induced with medazalam 0.1 mg/kg, fentanyl 10 microg/kg and vecuronium 0.1 mg/kg Administered intravenously. After tracheal intubation the patients were mechanically ventilated with pure oxygen. P(ET)CO2 was maintained between 35 approximately 45 mmHg. Anesthesia were maintained with fentanyl infusion combined with intermittent intravenous bolus of midazolam and vecuronium. MAP, CVP, HR, P(ET)CO2, SPO2, nasal and rectal temperature were monitored continuously. Remained dose of fentanyl was infused before the CPB. Blood Samples were taken before the operation (T1 ), before the CPB ( T2 ), 30 min after aortic declamping (T3 ) , 2 h after aortic declamping (T4 ), and 24 h (T5 ) after the operation for determination of plasma levels of tumor necrosis factor (TNF-alpha), interteukin IL-6 and IL-10, MDA. RESULTS: There was no significant change in the age, body weight, aortic cross-clomp time, CPB time, and operation time. Levels of TNF-alpha, IL-6, IL-10 and MDA after the CPB in the 3 groups were significantly higher compared with T, (P <0.01 ), TNF-alpha, IL-6 and MDA levels at T3, T4 were significantly lower in Group B and C than those in Group A. IL-10 levels at T4, T5 were significantly higher in Group B and C than those in Group A, but levels of TNF-alpha, IL-6, IL-10 and MDA in Group B were not significantly different compared with those in Group C. The duration of stay in the ICU and time of endotracheal extubation were significantly longer in patients of Group C than those of Group A and B. CONCLUSION: CPB leads to a proinflammatory and antiinflammatory response, as well as oxygen free radicals release. Larger dose fentanyl seemed to be effective in reducing CPB-induced inflammatory response and ischemic reperfusion injury, but the effect was not dependent on dose while fentanyl dose reaching some value, at the same time the duration of stay in ICU and time of endotracheal extubation is longer.

[Effects of ulinastatin on erythrocyte lipid peroxidation in patients undergoing open heart surgery].

OBJECTIVE: To investigate the effects of ulinastatin on erythrocyte lipid peroxidation in patients undergoing open heart surgery. METHODS: Twenty adult patients with rheumatic heart disease undergoing elective value replacement were divided randomly into 2 groups of 10 patients each: a control group (group C) and an ulinastatin group (group W). The patients were premedicated with intramuscular morphine 0.08 mg/kg and scopolamine 0.06 mg/kg. Anesthesia was induced with midazolam 0.1 mg/kg, fentanyl 5 microg/kg and vecuronium 0.1 mg/kg. After the tracheal intubation, the patients were mechanically ventilated. Anesthesia was maintained with midazolam, fentanyl and isoflurane. Blood samples were taken from radial artery before the operation (T1), 30 min after the initiation of CPB (T2), at the end of the CPB (T3), 30 min after the aorta declamping (T4) and 24 h after the operation (T5) for the determination of plasma and erythrocyte MDA (P-MDA and E-MDA) and erythrocyte SOD (E-SOD). RESULTS: The levels of P-MDA and E-MDA increased significantly after the initiation of CPB and the level of E-SOD was higher than the baseline level at T2, and then decreased from T3 to T5 in group C (P <0.001). The levels of P-MDA and E-MDA didn't increased until T4 (P <0.001) and returned to the baseline level at T5 in group W. The levels of P-MDA and E-MDA were significantly higher in group C than those in group W and the level of E-SOD was markedly lower than that in group W (P <0.05). CONCLUSION: Ulinastatin can alleviate erythrocyte lipid peroxidation in patients undergoing open heart surgery.