Spotted fever group Rickettsia(SFGR)are gram-negative,obligate intracellular pathogens that cause spotted fever rickettsiosis,a zoonotic disease.SFGR invade host cells through the expression of outer membrane proteins and Anaplasma-derived proteins.Then they use virulence factors,including phospholipases and cell surface antigens,to evade or suppress host immune de-fenses,thereby facilitating host colonization and intercellular dissemination,and exerting pathogenic effects.This review summarizes current research progress in various SFGR virulence factors,to further elucidate the pathogenic mechanisms of spotted fever rickettsio-sis,and provide a reference for the prevention and treatment of this disease.

Spotted fever group Rickettsia(SFGR)are gram-negative,obligate intracellular pathogens that cause spotted fever rickettsiosis,a zoonotic disease.SFGR invade host cells through the expression of outer membrane proteins and Anaplasma-derived proteins.Then they use virulence factors,including phospholipases and cell surface antigens,to evade or suppress host immune de-fenses,thereby facilitating host colonization and intercellular dissemination,and exerting pathogenic effects.This review summarizes current research progress in various SFGR virulence factors,to further elucidate the pathogenic mechanisms of spotted fever rickettsio-sis,and provide a reference for the prevention and treatment of this disease.

Objective:To identify the risk factors for acute lung injury (ALI) after pediatric living donor liver transplantation (LDLT) and evaluate the predictive value.Methods:The pediatric patients (all diagnosed with congenital biliary atresia) who underwent parental liver transplantation in our center from January to December 2021 were selected. Perioperative data were obtained through the electronic medical record system, and the pediatric patients were divided into non-ALI group and ALI group according to whether ALI occurred or not at 1 week after surgery. The factors of which P values were less than 0.05 between groups would enter the multivariate logistic regression analysis to stratify the risk factors for ALI after pediatric LDLT, and the value of the risk factors in predicting intraoperative ALI was evaluated using the receiver operating characteristic curve. Results:A total of 140 pediatric patients were enrolled in the analysis, and the incidence of ALI was 30.7%. The results of the multivariate logistic regression analysis showed that preoperative pediatric end-stage liver disease score, preoperative serum NT-pro-BNP concentrations, intraoperative volume of fluid transfused, and duration of postreperfusion syndrome were independent risk factors for ALI after LDLT in pediatric patients ( P<0.05). The area under the receiver operating characteristic curve of the preoperative N-terminal pro-brain natriuretic peptide(NT-pro-BNP) concentration in predicting postoperative ALI was 0.737 ( P<0.001), with a cutoff value of 222.1 ng/L, sensitivity of 0.628, and specificity of 0.732. Conclusions:Preoperative pediatric end-stage liver disease score, serum NT-pro-BNP concentrations, intraoperative volume of fluid transfused, and duration of postreperfusion syndrome are independent risk factors for ALI after LDLT in pediatric patients; preoperative serum NT-pro-BNP concentrations can effectively predict the development of ALI after pediatric LDLT surgery.

Objective:To evaluate the effect of stroke volume variation(SVV) goal-directed fluid therapy on postoperative pulmonary complications(PPCs) after pediatric living donor liver transplantation.Methods:One hundred and twenty pediatric patients undergoing pediatric living-donor liver transplantation(all diagnosed with congenital biliary atresia) were divided into 2 groups( n=60 each) using the random number table method: control group and SVV group. Intraoperative fluid management was guided by central venous pressure and mean arterial pressure in control group, while by SVV combined with cardiac output in SVV group. Intraoperative circulation, fluid intake and usage of vasoactive drug were recorded. Central venous blood samples were collected to determine the concentrations of serum Clara cell 16 kDa protein, interleukin-6, and tumor necrosis factor-alpha before anesthesia(T 0), at the end of anhepatic phase(T 1), at 3 h of neohepatic phase(T 2), at the end of surgery(T 3) and at 24 h after operation(T 4). Pulmonary ultrasonography was performed before surgery, at the end of surgery and at 1, 3 and 7 days after surgery. The pediatric patients were followed up for 1 week after surgery to record the PPCs, including acute lung injury, pulmonary infection, pulmonary atelectasis, pleural effusion and acute respiratory distress syndrome. Results:Compared with control group, the incidence of PPCs, acute lung injury and pulmonary infection was significantly decreased, the pulmonary ultrasound score was decreased at the end of surgery and at 1, 3 and 7 days after surgery, the usage of intraoperative dobutamine was increased, the duration of postreperfusion syndrome was shortened, the fluid intake and epinephrine usage were reduced, and the serum Clara cell 16 kDa protein, tumor necrosis factor-alpha and interleukin-6 concentrations were decreased at T 1-T 4 in SVV group( P<0.05). Conclusions:SVV goal-directed fluid management can reduce the development of PPCs in pediatric living donor liver transplantation.

Objective:To explore the barriers and facilitators for family members to inform elderly cancer patients of their condition.Methods:From August 2020 to September 2021, a total of family members of 16 elderly cancer patients admitted to the Renmin Hospital of Wuhan University were selected by convenient sampling. Semi-structured qualitative interview was conducted with the patients' family members. Colaizzi 7-step analysis method was used to analyze, sort out and refine the data.Results:A total of 8 themes were extracted. Barriers included integrating the patient's personality and experience to speculate the patient's acceptance, it was predicted that the sadness would be aggravated after being informed according to the current condition, lack of support and communication barriers. Facilitators included conjecture based on the patient's personality and willingness, there was a need to know the condition, maintaining family atmosphere and family culture and reference to relevant external information.Conclusions:There are many barriers and facilitators in the condition notification of elderly cancer patients. Medical and nursing staff and family members should not blindly conceal patients' condition. We should pay attention to patients' expression and respect their wishes, and provide personalized information and care strategies based on their past experience and current situation.

Objective:To explore the effect of intensive insulin therapy on hemodynamics and cardiac function in organ donors.Methods:A total of 60 organ donors were randomly divided into two groups of intensive insulin therapy(IIT)and control(30cases each group). Blood glucose was adjusted at 6.2~10.0 mmol/L in control group and 4.4~6.1 mmol/L in IIT group.Blood glucose and insulin dosage during maintenance were recorded.Cardiac function values as well as serum inflammatory factor concentrations at admission and during donation were compared between two groups.Results:During maintenance, blood glucose was significantly lower in IIT group than that in control group [(5.1±0.6)vs(8.2±1.5)mmol/L, P<0.05] and insulin dosage was higher than that in control group [(9.5±3.2)vs(5.8±1.5)U/h, P<0.05]. As compared with control group, cardiac cycle efficiency(CCE), maximal rate of elevated pressure(DP/DT max)and left ventricular ejection fraction(LVEF)in were significantly higher in IIT group than those of control group.And serum cardiac troponin I(cTnI), N-terminal B-type natriuretic peptide(NT-Pro-BNP), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)and high mobility group box-1 protein(HMGB1)as well as vasoactive-inotropic score(VIS)were significantly lower than those in control group( P<0.05). As compared with control group, cardiac donation rate of IIT group was significantly higher(30% vs 16.7%, P<0.05). Conclusions:Intensive insulin therapy and blood glucose control may blunt inflammatory response in organ donors, lessen myocardial injury and myocardial depression, stabilize hemodynamics and boost the rate of cardiac donation.

Objective:To evaluate the myocardial protective effect of goal-directed circulation management guided by cardiac index (CI) monitored by pressure recording analytical method (PRAM) in infants undergoing pediatric liver transplantation.Methods:A total of 120 pediatric patients, aged 5-15 months, weighing 5.5-10.0 kg, scheduled for elective living donor liver transplantation (all diagnosed with congenital biliary atresia) were selected and divided into 2 groups ( n=60 each) using a random number table method: routine group (group R) and goal-directed management guided by CI group (group CI-G). Patients in group R received routine hemodynamic monitoring according to central venous pressure (CVP), continuous invasive arterial pressure, blood gas analysis and other monitoring methods to guide intraoperative circulation management.Patients in CI-G group received intraoperative hemodynamic monitoring through radial artery using PRAM/Mostcare, and related treatments were guided by PRAM hemodynamic monitoring indicators.The intraoperative volume of fluid intake, highest and lowest values of parameters of hemodynamics such as heart rate (HR), mean arterial pressure (MAP) and CVP, the maximum fluctuations (△ RHR, △ RMAP and △ RCVP) and the development of reperfusion syndrome within 5 min of reperfusion were recorded.At the beginning of anesthesia (T 0), at 5 min before reperfusion (T 1), at 30 min of neohepatic phase (T 2), at 3 h of neohepatic phase (T 3) and at 12 h after operation (T 4), concentrations of serum cardiac troponin I (cTnI), N-terminal plasma brain natriuretic peptide precursor (NT-pro-BNP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and high mobility group protein B1 (HMGB1) were determined.Mechanical ventilation time, duration of intensive care unit (ICU) stay, the development of heart failure and pulmonary infection, length of hospital stay were recorded. Results:Compared with group R, the intraoperative volume of fluid intake, highest value of CVP, △ RHR, △ RMAP and the incidence of reperfusion syndrome were significantly decreased, lowest value of MAP was increased, concentrations of serum cTnI, NT-pro-BNP, IL-6, TNF-α and HMGB1 was decreased, mechanical ventilation time and duration of ICU were shortened, and the incidence of heart failure during ICU stay were decreased in group CI-G( P<0.05). Conclusion:The goal-directed circulation management guided by CI monitored by PRAM can accurately guide the use of volume and vasoactive drugs, stabilize circulation, which can produce myocardial protective effect to some extent in infants undergoing pediatric liver transplantation.

Objective:To explore the effect of cardiac output-guided hemodynamic management on acute kidney injury(AKI)during pediatric liver transplantation.Methods:A total of 120 pediatric living-donor liver transplantation recipients were randomly divided into two groups of control and experiment(60 cases each group). Control group received routine hemodynamic management of central venous pressure(CVP), continuous invasive arterial pressure and blood gas analysis.Experiment group was subjected to cardiac output-guided hemodynamic management guided by cardiac index, stroke volume index, stroke volume variation and left ventricular contractility index (DP/DTmax). Intraoperative hemodynamics and incidence of AKI were recorded.And the serum changes of neutrophil gelatinase-associated lipocalin(NGAL), cystatin C(CysC)and inflammatory factors were analyzed.Results:The incidence of AKI was lower in experiment group than that in control group(26.7% vs 45%). The incidence of postreperfusion syndrome(PRS), intraoperative fluid infusion and maximal value of CVP were lower while minimal value of mean arterial pressure(MAP)higher in experiment group than those in control group( P<0.05). The serum levels of NGAL, CysC, interleukin-6(IL-6), interleukin-18(IL-18)and tumor necrosis level-alpha(TNF-α)were lower in experiment group than those in control group at each timepoint from 3 h post-reperfusion to 48 h post-operation( P<0.05). Conclusions:During pediatric living-donor liver transplantation, cardiac output-guided hemodynamic management is conducive to more accurate fluid management.It can stabilize circulation, minimize PRS and reduce the occurrence of AKI during perioperative period.

Objective: To investigate the effect of manganese chloride (MnCl₂) or 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) on the neurobehavioral and histopathology in C57BL/6 mice and provide evidence for the diagnosis, treatment and prevention of manganism. Methods: Adult male C57BL/6 mice were treated with MnCl₂ and MPTP respectively by intraperitoneal injection at the doses of 5, 10, 20mg Mn/kg and 30mg MPTP/kg. Controls were injected equivalent normal saline. All animals were administrated 5 times a week for 4 consecutive weeks and sacrificed after behavior tests on the fifth week. Balance ability, anxiety and depression level and cognitive function were tested respectively by vertical pole test, open field locomotion test and Morris swim task. The neuron pathological changes of striatum and substantia nigra were examined through HE-staining pathological section by using optical microscope. Results: Compared with the control group, the high dose of MnCl₂ reduced body weight obviously (P<0.01) . The results of vertical pole test showed that MnCl₂ and MPTP lengthened the pole-climbing time and turnaround time. Open field locomotion test showed that movement distance, stand-up time and central field time were decreased after the exposure of MnCl₂ or MPTP. In the Morris swim task, the escape latency time increased and the target quadrant activity time decreased significantly after the injection of MPTP as well as high-dose MnCl₂, comparing with controls (P<0.05) . Moreover, the escape latency time of high dose MnCl₂ prolonged prominently comparing with MPTP grou (P<0.05) . The results of histopathology showed that acidophilic changes elevated in MnCl₂ and MPTP group, comparing with controls. Furthermore, in striatum the oxyphil cells number increased in MnCl₂ high-dose group comparing with MPTP group (P<0.01) . On the contrary, there were more oxyphil cells in MPTP group comparing with MnCl₂ groups in substantia nigra (P<0.01) . Conclusion Both manganese and MPTP can induce the impairment of dopaminergic neural system, but the symptons and injured location of manganism are inconsistent with PD models induced by MPTP.

Objective: To investigate the effect of manganese chloride (MnCl₂) or 1-methyl-4-phenylpyridinium (MPP ⁺) on oxidative stress and autophagy in human neuroblastomaSK-N-SH cells and the mechanism of the neurotoxicity of manganese. Methods: SK-N-SH cells were treated with MnCl₂ or MPP⁺ at doses of 0.062 5, 0.125, 0.25, 0.5, 1.0, and 2.0 mmol/L for 24 hours, and MTT assay was used to measure cell viability. The cells weretreated with MnCl₂ or MPP⁺ at doses of 0.125, 0.25, and 0.5 mmol/L for 24 hours, and flow cytometry was used to measure the content of reactive oxygen species (ROS) in cells, a laser scanning confocal microscope was used to observe autophagosome in cells, and Western blot was used to measure the expression of autophagy-related proteins P62 and LC3-II/LC3-I. Results: Compared with the control group, the 0.0625-2.0 mmol/L MnCl₂ and 0.125-2.0 mmol/L MPP ⁺ treatment groups had significant reductions in the viability of SK-N-SH cells, and the 0.25-2.0 mmol/L MnCl₂ treatment groups had significantly lower viability than the groups treated with the same doses of MPP⁺ (all P<0.05) . Compared with the control group, the 0.125-0.25 mmol/L MnCl₂ and 0.125-0.5 mmol/L MPP⁺ treatment groups had significant increases in the content of ROS, and the 0.25-0.5 mmol/L MPP⁺ treatment groups had significantly higher content of ROS than the groups treated with the same doses of MnCl₂ (all P<0.05) . Compared with the control group, the 0.25-0.5 mmol/L MnCl₂ andMPP⁺ treatment groups had significant increases in autophagy-related proteins LC3-II/LC3-I and significant reductions in P62 expression; the 0.125-0.5 mmol/L MPP⁺ treatment groups had significantly higher LC3-II/LC3-I than the groups treated with the same doses of MnCl₂, and the 0.125 and 0.25 mmol/L MPP ⁺ treatment groups had significantly lower P62 expression than the groups treated with the same doses of MnCl₂ (all P<0.05) . Conclusion Both MnCl₂ and MPP⁺ can induce oxidative stress and autophagy in SK-N-SH cells, and MPP⁺ has a significantly greater inductive effect on autophagy of SK-N-SH cells than MnCl₂.