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Objective:To explore the correlation between intraoperative regional cerebral oxygen saturation(rScO 2) and nerve damage markers with postoperative neurological dysfunction(PND) in patients undergoing acute Stanford type A aortic dissection surgery. Methods:A total of 57 patients undergoing acute Stanford type A aortic dissection surgery under cardiopulmonary bypass(CPB) in the operating room of Henan Provincial Hospital from July 2020 to May 2021 were enrolled, regardless of gender, aged 35-64 years old, weighed 58.0-90.0 kg and with American Association of Anesthesiologists(ASA) classification status with Ⅱ-Ⅲ. A near infrared spectrometer(NIRS) was used to continuously monitor the bilateral rScO 2 of the patients during the surgery. Central venous blood was drawn 10 min before induction of anesthesia(T0), 10 min after induction of anesthesia(T1), immediately after CPB started(T2), when CPB ended(T3), at the end of the operation(T4), and when exiting ICU(T5), 1 day(T6), 2 days(T7) and 3 days(T8) after operation, and the levels of nerve injury marker S100 calcium binding protein(S100β protein) and neuron-specific enolase(NSE) in serum were measured. Follow up was performed on postoperative 3 to evaluate the occurrence of PND.The value of intraoperative rScO 2 and the concentrations serum S100β protein and NSE were compared between the PND group and the NND(NPND) group. The changes of intraoperative rScO 2 value, the concentrations of serum S100β protein and NSE between the PND group and NPND group were compared. The risk factors of PND and its correlation with the intraoperative rScO 2 value, and the concentrations of serum S100β protein and NSE were analyzed. The prognostic indicators of the two groups of patients were statistically analyzed. Results:Three patients were excluded from the study. A total of 12 patients(22.2%) developed PND(PND group), and 42 patients(77.8%) did not develop PND(NPND group) on postoperative 3 day. Compared with the NPND group, the minimum mean arterial pressure and the minimum rScO 2 during CPB were significantly decreased( P<0.05), the maximum da-rScO 2 during CPB was significantly increased( P<0.05), and duration of da-rScO 2>0.50, duration of da-rScO 2>0.40, duration of rScO 2 reduction >25%, rScO 2<0.50, rScO 2<0.40, during CPB were significantly prolonged( P<0.05) in the PND group. The levels of serum S100β and NSE in the PND group were significantly increased, compared with the NPND group at T2-8, respectively. Logistic regression analysis showed that the reduction of rScO 2 more than 25%( P=0.033), during of rScO 2<0.40( P=0.007) and duration of da-rScO 2>0.50( P=0.001) during CPB were risk factors of PND. Conclusion:Compared with the NPND group, the postoperative mechanical ventilation time, duration of ICU stay, postoperative hospital stay and PND recovery time were significantly prolonged( P<0.05), and the medical expenses were increased significantly( P<0.05) in the PND group. The duration of the reduction of rScO 2>25%, the duration of rScO 2<0.40 and the duration of da-rScO 2>0.50 during CPB are the risk factors of PND in patients with acute Stanford type A aortic dissection under CPB. Significantly increased levels of serum nerve injury markers S100β and NSE are related to the occurrence of PND. The occurrence of PND has a significant adverse effect on the early clinical prognosis of patients.
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Neutralizing antibodies (NAbs) can prevent and treat infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, continuously emerging variants, such as Omicron, have significantly reduced the potency of most known NAbs. The selection of NAbs with broad neutralizing activities and the identification of conserved critical epitopes are still urgently needed. Here, we identified an extremely potent antibody (55A8) by single B-cell sorting from convalescent SARS-CoV-2-infected patients that recognized the receptor-binding domain (RBD) in the SARS-CoV-2 spike (S) protein. 55A8 could bind to wild-type SARS-CoV-2, Omicron BA.1 and Omicron BA.2 simultaneously with 58G6, a NAb previously identified by our group. Importantly, an antibody cocktail containing 55A8 and 58G6 (2-cocktail) showed synergetic neutralizing activity with a half-maximal inhibitory concentration (IC50) in the picomolar range in vitro and prophylactic efficacy in hamsters challenged with Omicron (BA.1) through intranasal delivery at an extraordinarily low dosage (25 g of each antibody daily) at 3 days post-infection. Structural analysis by cryo-electron microscopy (cryo-EM) revealed that 55A8 is a Class III NAb that recognizes a highly conserved epitope. It could block angiotensin-converting enzyme 2 (ACE2) binding to the RBD in the S protein trimer via steric hindrance. The epitopes in the RBD recognized by 55A8 and 58G6 were found to be different and complementary, which could explain the synergetic mechanism of these two NAbs. Our findings not only provide a potential antibody cocktail for clinical use against infection with current SARS-CoV-2 strains and future variants but also identify critical epitope information for the development of better antiviral agents.
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Following Delta, Omicron variant triggered a new wave of SARS-CoV-2 infection globally, adaptive evolution of the virus may not stop, the development of broad-spectrum antivirals is still urgent. We previously developed two hetero-bivalent nanobodies with potent neutralization against original WT SARS-CoV-2, termed aRBD-2-5 and aRBD-2-7, by fusing aRBD-2 with aRBD-5 or aRBD-7, respectively. Here, we resolved crystal structures of these nanobodies in complex with RBD, and found the epitope of aRBD-2 differs from that of aRBD-5, aRBD-7. aRBD-2 binds to a conserved epitope which renders its binding activity to all variants of concern (VOCs) including Omicron. Interestingly, although monovalent aRBD-5 and aRBD-7 lost binding to some variants, they effectively improved the overall affinity when transformed into the hetero-bivalent form after being fused with aRBD-2. Consistent with the high binding affinities, aRBD-2-5-Fc and aRBD-2-7-Fc exhibited ultra-potent neutralization to all five VOCs; particularly, aRBD-2-5-Fc neutralized authentic virus of Beta, Delta and Omicron with the IC50of 5.98[~]9.65 ng/mL or 54.3[~]87.6 pM. Importantly, aRBD-2-5-Fc provided in vivo prophylactic protection for mice against WT and mouse-adapted SARS-CoV-2, and provided full protection against Omicron in hamster model when administrated either prophylactically or therapeutically. Taken together, we found a conserved epitope on RBD, and hetero-bivalent nanobodies had increased affinity for VOCs over its monovalent form, and provided potent and broad-spectrum protection both in vitro and in vivo against all tested major variants, and potentially future emerging variants. Our strategy provides a new solution in the development of therapeutic antibodies for COVID-19 caused by newly emergent VOCs.
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SARS-CoV-2 has infected more than 400 million people around the globe and caused millions of deaths. Since its identification in November 2021, Omicron, a highly transmissible variant, has become the dominant variant in most countries. Omicrons highly mutated spike protein, the main target of vaccine development, significantly compromises the immune protection from current vaccination. We develop an mRNA vaccine (SOmicron-6P) based on an Omicron-specific sequence. In mice, SOmicron-6P shows superior neutralizing antibodies inducing abilities to a clinically approved inactivated virus vaccine, a clinically approved protein subunit vaccine, and an mRNA vaccine (SWT-2P) with the same sequence of BNT162b2 RNA. Significantly, SOmicron-6P induces a 14.4[~]27.7-fold and a 28.3[~]50.3-fold increase of neutralizing activity against the pseudovirus of Omicron and authentic Omicron compared to SWT-2P, respectively. In addition, two doses SOmicron-6P significantly protects Syrian hamsters against challenge with SARS-CoV-2 Omicron variant and elicits high titers of nAbs in a dose-dependent manner in macaques. Our results suggest that SOmicron-6P offers advantages over current vaccines, and it will be helpful for those with weak immunity.
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Objective:To evaluate the effect of apneic oxygen insufflation (AOI) on phenotypic transformation of alveolar macrophage (AM) in the non-ventilated lung during one-lung ventilation (OLV).Methods:A total of 60 patients of either sex, aged 40-64 yr, weighing 45-85 kg, undergoing elective thoracoscopic lobectomy, were recruited and divided into 2 groups using a computer-generated table of random numbers: test group and control group, with 30 cases in each group.At the beginning of OLV, the non-ventilated lung received 3 L/min of AOI in test group and no AOI in control group.Radial artery blood samples were collected for blood gas analysis before operation, immediately after anesthesia induction, 30 min, 1 h and 2 h after the start of OLV, and oxygenation index (OI) was calculated.The resected normal lung tissues around the lung lobe were excised at 2 h after the start of OLV for microscopic examination of the pathological changes after HE staining, and the lung injury score was assessed.Bronchoalveolar lavage fluid (BALF) was collected at 2 h after the start of OLV, AM was sorted by flow cytometry, and the apoptotic rate was calculated.The levels of intracellular Ca 2+ and reactive oxygen species (ROS, a marker of M1 AM phenotype) in cells were determined.The concentrations of M1 phenotype AM markers inducible nitric oxide synthase (iNOS), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) and of M2 phenotype AM markers arginase 1 (Arg-1) and interleukin 10 (IL-10) in BALF were measured by enzyme-linked immunosorbent assay. Results:Compared with control group, SpO 2, PaO 2 and OI were significantly increased, PaCO 2 and lung injury score were decreased, the survival rate of AM was increased, the apoptotic rate in the early and late stages was decreased, the concentrations of iNOS, IL-6 and TNF-α in BALF were decreased, and the concentrations of Arg-1 and IL-10 in BALF were increased, the level of ROS in AM was decreased, and the level of Ca 2+ in AM was increased in test group ( P<0.05). Conclusions:The mechanism by which implementing AOI in the non-ventilated lung reduces lung injury may be related to promotion of transformation of AM from M1 phenotype to M2 phenotype and inhibition of inflammatory responses during OLV in the patients undergoing thoracoscopic lobectomy.
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ObjectiveTo establish a rapid screening method for germplasm materials of Gastrodia elata with high purity， and lay a foundation for pure line breeding and cross breeding. MethodBased on the whole genome sequencing and population resequencing of G. elata， 20 restriction fragment length polymorphism (RFLP) markers were developed by single nucleotide polymorphism (SNP) sites. The polymerase chain reaction (PCR)-RFLP method was used to carry out restriction endonuclease experiments on 20 RFLP markers of 15 G. elata germplasms. According to the number of enzymatic bands at 20 RFLP marker sites, the purity of 15 germplasms was calculated and evaluated. On this basis, genome resequencing technology was used to verify the assessment results. ResultTen germplasm materials with purity greater than 95% were screened out by PCR-RFLP method， 3 of which had 95% purity and 7 had 100% purity. Nine germplasm materials with purity greater than 95% were screened out by genome resequencing methods, and 8 of them were consistent with the results of PCR-RFLP. ConclusionThe PCR-RFLP method established in this study for screening G. elata germplasms with high purity precision of RFLP markers has 80% precision and 89% accuracy. The method is simple， efficient， and significantly less expensive than genome resequencing method, which provides technical support for pure line breeding of G. elata and references for breeding of other Chinese medicinal materials.
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Objective:To evaluate the relationship between postoperative delirium (POD) and pyroptosis of peripheral blood mononuclear cells (PBMCs) in the patients undergoing heart valve replacement with cardiopulmonary bypass (CPB).Methods:Sixty patients of either sex, aged 45-64 yr, with body mass index of 18-25 kg/m 2, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with New York Heart Association class Ⅱ or Ⅲ, undergoing elective heart valve replacement with CPB, were enrolled in this study.POD was assessed by the Consciousness Assessment Method for the intensive care unit (CAM-ICU) within 3 days after operation.All the patients were divided into 2 groups according to whether POD occurred within 3 days after operation: POD group ( n=45) and non-POD group (NPOD group, n=15). After induction of anesthesia and before skin incision (T 1), at 30 min after start of CPB (T 2), immediately after termination of CPB (T 3) and at 24 h after termination of CPB (T 4), blood samples from the internal jugular vein were collected to determine the concentrations of plasma S100β, neuron-specific enolase (NSE), interleukin (IL)-18 and IL-1β (by enzyme-linked immunosorbent assay) and expression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), caspase-1 and gasdermin D (GSDMD) in PBMCs (by Western blot). The postoperative mechanical ventilation time and length of stay in ICU were recorded. Results:Compared with NPOD group, the concentrations of plasma S100β, NSE, IL-18 and IL-1β were significantly increased, the expression of NLRP3, caspase-1 and GSDMD in PBMCs was up-regulated at T 2-4, and the postoperative mechanical ventilation time and length of stay in ICU were prolonged in POD group ( P<0.05). Compared with those at T 1, the concentrations of plasma S100β, NSE, IL-18 and IL-1β were significantly increased, and the expression of NLRP3, caspase-1 and GSDMD in PBMCs was up-regulated at T 2-4 in POD and NPOD groups ( P<0.05). Conclusion:The occurrence of POD may be associated with the pyroptosis of PBMCs in patients undergoing heart valve replacement with CPB.
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Objective:To evaluate the effect of remote ischemic preconditioning (RIPC) combined with postconditioning (RIPostC) on postoperative pulmonary complications in elderly patients undergoing thoracoscopic radical surgery for lung cancer.Methods:Eighty American Society of Anesthesiologists physical status Ⅱ or Ⅲ elderly patients, aged 65-79 yr, with height 155-180 cm, weighing 45-80 kg, were divided into 2 groups ( n=40 each) by the random number table method: control group (group C) and RIPC combined with RIPostC group (group R). RIPC was induced by 3 cycles of 5 min ischemia (cuff inflation to 200 mmHg) followed by 5 min reperfusion (cuff deflation to 0 mmHg) though applying a mercury sphygmomanometer adult cuff to the right upper extremity at 30 min before one-lung ventilation and 30 min before the end of one-lung ventilation in group R. The adult cuff was only bound to the right upper extremity without inflation and deflation in group C. The occurrence of pulmonary complications was recorded within 72 h after operation in both groups.The Quality of Recovery-15 score was used to assess the early postoperative quality of recovery on 1 and 2 days after operation.The number of white blood cells and neutrophils and percentage of neutrophils were recorded at 1 day before surgery and 1 and 3 days after surgery.The postanesthesia care unit stay time and hospital stay time were recorded. Results:Compared with group C, the incidence of pulmonary complications was significantly decreased within 72 h after operation, Quality of Recovery-15 scores were increased at 1 and 2 days after operation, the number of white blood cells and neutrophils and percentage of neutrophils were decreased at 1 and 3 days after operation, and the postanesthesia care unit stay time and postoperative hospital stay time were shortened in group R ( P<0.05). Conclusion:RIPC combined with RIPostC can decrease the risk of postoperative pulmonary complications and is helpful for early postoperative rehabilitation in elderly patients undergoing thoracoscopic radical surgery for lung cancer.
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Objective To evaluate the effects of remote ischemic preconditioning (RIPC) on occurrence of postoperative delirium in elderly patients undergoing radical mastectomy.Methods Sixty elderly patients,aged 65-78 yr,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,scheduled for elective radical mastectomy,were allocated into 2 groups (n =30 each) using a random number table method:control group (group C) and RIPC group.Three cycles of 5-min ischemia/5-min reperfusion induced by a blood pressure cuff placed on the upper arm of the right upper arm served as RIPC treatment at 5 min after induction of anesthesia in RIPC group.The blood pressure cuff was only placed on the upper arm of the right upper arm without inflation and deflation in group C.Jugular bulb venous blood samples were obtained at 10 min before anesthesia induction (T0) and 1,12,24,48 and 72 h after the end of operation (T1-5) for determination of S-100β protein and neuron-specific enolase (NSE) concentrations in serum.The occurrence of delirium within 72 h after operation was estimated using Confusion Assessment Method for the Intensive Care Unit.The occurrence of hypotension,sinus bradycardia and reintubation was recorded.The Quality of Recovery-15 (QoR-15) was used to evaluate the early postoperative quality of recovery at 1 and 2 days after operation.Results Compared with group C,the concentrations of S-100β protein and NSE in serum and incidence of delirium within 72 h after operation were significantly decreased at T1-T5,and the Quality of Recovery-15 scores were increased at 1 and 2 days after operation in group RIPC (P＜0.05).There was no significant difference in the duration of delirium or incidence of hypotension,sinus bradycardia and reintubation between the two groups (P＞0.05).Conclusion RIPC can decrease the development of postoperative delirium and is helpful for the early postoperative recovery of elderly patients undergoing radical mastectomy.
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Objective@#To evaluate the effects of remote ischemic preconditioning (RIPC) on occurrence of postoperative delirium in elderly patients undergoing radical mastectomy.@*Methods@#Sixty elderly patients, aged 65-78 yr, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, scheduled for elective radical mastectomy, were allocated into 2 groups (n=30 each) using a random number table method: control group (group C) and RIPC group.Three cycles of 5-min ischemia/5-min reperfusion induced by a blood pressure cuff placed on the upper arm of the right upper arm served as RIPC treatment at 5 min after induction of anesthesia in RIPC group.The blood pressure cuff was only placed on the upper arm of the right upper arm without inflation and deflation in group C. Jugular bulb venous blood samples were obtained at 10 min before anesthesia induction (T0) and 1, 12, 24, 48 and 72 h after the end of operation (T1-5) for determination of S-100β protein and neuron-specific enolase (NSE) concentrations in serum.The occurrence of delirium within 72 h after operation was estimated using Confusion Assessment Method for the Intensive Care Unit.The occurrence of hypotension, sinus bradycardia and reintubation was recorded.The Quality of Recovery-15 (QoR-15) was used to evaluate the early postoperative quality of recovery at 1 and 2 days after operation.@*Results@#Compared with group C, the concentrations of S-100β protein and NSE in serum and incidence of delirium within 72 h after operation were significantly decreased at T1-T5, and the Quality of Recovery-15 scores were increased at 1 and 2 days after operation in group RIPC (P<0.05). There was no significant difference in the duration of delirium or incidence of hypotension, sinus bradycardia and reintubation between the two groups (P>0.05).@*Conclusion@#RIPC can decrease the development of postoperative delirium and is helpful for the early postoperative recovery of elderly patients undergoing radical mastectomy.
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Objective To investigate the blood-saving effect of tranexamic acid in patients undergoing Stanford type A aortic dissection surgery.Methods Fifty-six patients of both sexes with acute Stanford type A aortic dissection, aged 34-58 yr, weighing 62-84 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ , with their left ventricular ejection fraction ＞ 40％, undergoing emergency surgery, were randomly divided into 2 groups: control group (group C, n=26) and tranexamic acid group (group TA, n=30).Tranexamic acid was infused as a bolus of 10 mg/kg over 30 min before skin incision followed by an infusion of 10 mg · kg-1 · h-1 throughout the surgery in group TA.The equal volume of normal saline was given instead in group C.The total volume of drainage at 24 h after operation, the postoperative requirement of allogeneic red blood cells, fresh frozen plasma and platelets, and re-thoracotomy for bleeding were recorded.The postoperative mechanical ventilation time, duration of intensive care unit stay, and complications after operation were also recorded.Results Compared with group C, the total volume of drainage at 24 h after operation, and the requirement of allogeneic red blood cells, fresh frozen plasma and platelets were significantly reduced, the incidence of rethoracotomy for bleeding was decreased, the postoperative mechanical ventilation time, and duration of intensive care unit stay were shortened, and the incidence of postoperative acute lung injury and transient neurological dysfunction were decreased in group TA.Conclusion Tranexamic acid has blood-saving effect and can reduce postoperative bleeding and allogeneic blood transfusion in patients undergoing Stanford type A aortic dissection surgery.
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Objective To evaluate the effect of small interfering RNA targeting caspase-12 (caspase-12-siRNA) pretreatment on lung ischemia/reperfusion (I/R) injury in mice.Methods Forty male C57BL/6J mice,aged 6-8 weeks,weighing 16-24 g,were randomly allocated into 4 groups (n =10 each) using a random number table:sham operation group (group S),group I/R,negative control group (group NC) and caspase-12-siRNA pretreatment group (group siRNA).Lung I/R was induced by clamping the left pulmonary hilum for 30 min followed by 3 h reperfusion in anesthetized mice in IR,NC and siRNA groups.At 48 h before ischemia,negative control siRNA 20 μg and caspase-12-siRNA 20 μg were instilled intranasally in NC and siRNA groups,respectively,and the total volume was 50 μl.At 3 h of reperfusion,the animals were sacrificed and the left lung was removed for determination of wet/dry lung weight (W/D) ratio and lung water content in lung tissues and for microscopic examination.Pulmonary ultrastructure was examined with electron microscope.The quantitative evaluation index (QEI) for alveolar damage and apoptosis rate were calculated.Results Compared with group S,W/D ratio,lung water content,QEI for alveolar damage and apoptosis index were significantly increased in IR and NC groups,QEI for alveolar damage and apoptosis index were increased in group siRNA (P ＜ 0.05).Compared with IR and NC groups,W/D ratio,lung water content,QEI for alveolar damage and apoptosis index were significantly decreased (P ＜ 0.05),and the pathological changes of lungs were alleviated in group siRNA.There was no significant difference in the indices mentioned above between groups IR and NC (P ＞ 0.05).Conclusion Caspase-12-siRNA pretreatment can attenuate lung I/R injury in mice.
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Objective: To establish the GC fingerprints of essential oil for Schizonepeta tenuifolia Briq. to control the quality. Methods:The temperature of the feed inlet and detector was both 250℃, the carrier gas was nitrogen, and the flow rate was 2 ml· min-1 . The essential oil from ten batches of Schizonepeta tenuifolia Briq. was analyzed by GC-MS to determine the characteristic peaks and the similarity was studied as well. Results:The GC fingerprints of essential oil from Schizonepeta tenuifolia Briq. was established, and totally 13 characteristic peaks were calibrated with high similarity. Conclusion: The method is simple, precise and reliable. The established fingerprints can be used as one of the quality control index for essential oil from Schizonepeta tenuifolia Briq. .
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ObjectiveTo research the hepatitis B virus (HBV) replication and immune tolerance status of transgenic mice for elucidating the pathogenesis of hepatitis B and evaluating new drugs against HBV.Methods SPE grade HBsAg negative nontransgenic and transgenic mice with the same genetic background were recruited in this study.HBsAg,HBeAg and HBV DNA were detected by chemiluminescent method.Pre-S1 and HBcAg were detected by enzyme linked immunosorbont assay (ELISA).Liver pathology was examined and HBsAg expressions at different stages were determined by immunohistochemical staining.The lymphocyte proliferation of mice was detected by flow cytometry and interferon (IFN)γ-producing T lymphocytes was determined by enzyme linked immunospot (ELISPOT).The expressions of Toll-like receptor (TLR)2 and TLR9 in splenocyte suspension and splenic dendrite cells (DC) were determined by double-labeling immunofluorescence.The data were analyzed by t test and F test.ResultsHBsAg,preS1,HBeAg,HBcAg were expressed and HBV DNA was replicated in HBV transgenic mice,while anti-HBs,anti-HBc,and anti-HBe were all negative.There were no obvious pathological changes in liver tissues.HBsAg was expressed in cytoplasm and HBcAg in nucleus of hepatocytes.After stimulated with HBsAg,T lymphocyte proliferation capacity of HBV transgenic mice was (697.6±67.3) cpm,which was much lower than that of nontransgenic mice [( 1315.5 ±191.6) cpm].The number of spot forming cells of IFNγ-producing splenocytes from transgenic mice after HBsAg stimulation was 8.25 ± 1.10,which was obviously lower than that of nontransgenic mice (28.50±4.21) (F=155.967,P=0.000).The expressions of CD11c+,TLR2 and TLR9 on DC from both HBV transgenic and nontransgenic mice were not different significantly (all P＞0.05).The HBsAg expressions in liver tissues were observed in 18-day-old fetal mice and 1-day-old newborn mice.ConclusionsThe HBV transgenic mice can express HBV-related antigens,and are immune tolerant to the antigens.The innate and acquired immunity of the HBV transgenic mice are normal,which is similar to chronic asymptomatic HBV carriers of human.Therefore,HBV transgenic mouse is an ideal animal model.
