Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

This article aims to explore the effect and mechanism of Liujunzi Pills on the intestinal microbiota of rats with spleen Qi deficiency syndrome. The raw Rhei Radix et Rhizoma water extract(1 g·mL~(-1)) was used to prepare spleen Qi deficiency rat models. A total of 44 SD male rats were randomly divided into a control group, a model group, Liujunzi Pills groups at high(3.24 g·kg~(-1)), medium(1.62 g·kg~(-1)), low(0.81 g·kg~(-1)) doses, and Shenling Baizhu San(2.50 g·kg~(-1)) group. The drug effect was evaluated by observing the following aspects: spleen index, fecal water content, body weight, and intestinal propulsion index. Gut microbiota analysis and 16S rRNA gene sequencing were conducted on feces. Enzyme-linked immunosorbent assay(ELISA) and UV spectrophotometry were used to detect interleukin-1β(IL-1β) and adenosine triphosphate(ATP) levels in small intestine tissues. Hematoxylin-eosin staining and transmission electron microscopy were employed to observe changes in intestinal pathology and microstructure. The results show that, compared with the control group, fecal moisture content is significantly increased while spleen index, body weight, and intestinal propulsion index are significantly reduced in rats of the model group, indicating the successful establishment of the model. The above symptoms can be improved by both Shenling Baizhu San and Liujunzi Pills. Compared with the control group, in the model group, the gut microbiota abundance is changed with an unbalanced development: the abundance of beneficial bacteria within the Bacteroidetes phylum is reduced, accompanied by a significantly decreased Shannon index, and reduced signal levels of nicotinamide adenine dinucleotide phosphate(NADPH)-related enzymes relevant to mitochondria. However, Liujunzi Pills and Shenling Baizhu San can significantly improve the Bacteroidetes phylum abundance in gut microbiota, microbial diversity, and NADPH activity in the model group. Additionally, compared with the control group, the ATP level is decreased and the IL-1β level is increased in small intestinal tissues of the model group, with shorter small intestinal epithelial villi and decreased mitochondrial number. The above symptoms can be improved by Liujunzi Pills and Shenling Baizhu San. In conclusion, Liujunzi Pills can treat spleen Qi deficiency syndrome by enhancing mitochondrial function to regulate gut microbiota balance and diversity.
Animals ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Rats, Sprague-Dawley ; Rats ; Qi ; Spleen/metabolism* ; Splenic Diseases/metabolism* ; Humans ; Interleukin-1beta/genetics* ; Bacteria/drug effects* ; Feces/microbiology* ; Adenosine Triphosphate/metabolism*

The protein kinase A/protein kinase G/protein kinase C-family (AGC kinase family) of eukaryotes is involved in regulating numerous biological processes. The 3-phosphoinositide- dependent protein kinase 1 (PDK1), is a conserved serine/threonine kinase in eukaryotes. To understand the roles of PDK1 homologous genes in cell death and immunity in tetraploid Nicotiana tabacum, the previuosly generated transgenic CRISPR/Cas9 lines, in which 5-7 alleles of the 4 homologous PDK1 genes (NtPDK1a/1b/1c/1d homologs) simultaneously knocked out, were used in this study. Our results showed that the hypersensitive response (HR) triggered by transient overexpression of active Pto (Pto^Y207D) or soybean GmMEKK1 was significantly delayed, whereas the resistance to Pseudomonas syrangae pv. tomato DC3000 (Pst DC3000) and tobacco mosaic virus (TMV) was significantly elevated in these partial knockout lines. The elevated resistance to Pst DC3000 and TMV was correlated with the elevated activation of NtMPK6, NtMPK3, and NtMPK4. Taken together, our results indicated that NtPDK1s play a positive role in cell death but a positive role in disease resistance, likely through negative regulation of the MAPK signaling cascade.
Nicotiana/virology* ; Disease Resistance/genetics* ; Plant Diseases/immunology* ; Plants, Genetically Modified/genetics* ; Gene Knockout Techniques ; Plant Proteins/genetics* ; CRISPR-Cas Systems ; Protein Serine-Threonine Kinases/genetics* ; 3-Phosphoinositide-Dependent Protein Kinases/genetics* ; Pyruvate Dehydrogenase Acetyl-Transferring Kinase ; Tobacco Mosaic Virus/pathogenicity*

Objective To explore the protective effect of L-carnitine on myocardial systolic dysfunction in sepsis and its underlying mechanism.Methods A mouse sepsis model was established by cecal ligation and puncture(CLP).Ten-week-old male SPF-grade C57BL/6 mice(body weight 20～30 g)were randomly divided into 5 groups via random number table:Sham group,Sepsis group,L-carnitine group,L-carnitine+Etomoxir(Eto)group,and Eto group.Echocardiography assessed cardiac function,ELISA measured serum creatine kinase isoenzyme MB(CK-MB)levels,and 72-hour survival rates were recorded to evaluate L-carnitine's effects on cardiac function.Cardiomyocytes were isolated,and a cell microtensiometer was used to detect cardiomyocyte contractile function and calcium transients.Myocardial tissues were collected from each group,and ELISA was used to determine the contents of triglyceride(TG),free fatty acid(FFA),and adenosine triphosphate(ATP).An in vitro sepsis model was constructed by stimulating HL-1 cardiomyocytes with lipopolysaccharide(LPS)for 12 hours,which was divided into 5 groups:control(CTRL)group,LPS group,L-carnitine group,L-carnitine+Eto group,and Eto group.ELISA was used to detect the contents of TG,FFA,and ATP as well as the activity of carnitine palmitoyltransferase 1A(CPT1A)in cardiomyocytes.A cellular energy metabolism analysis system was employed to measure fatty acid oxidation capacity,and Western blot was used to detect the protein expression of CPT1A in cardiomyocytes.BODIPY-FL-C16(green fluorescently labeled palmitic acid)was utilized to detect the distribution of fatty acids in the cytoplasm and mitochondria via immunofluorescence technology,thereby observing the ability of cells to transport fatty acids into mitochondria.Results Compared with the Sham group,cardiac function was significantly impaired in the Sepsis group,as evidenced by decreased ejection fraction and mean arterial pressure(P<0.05),along with elevated levels of the cardiac injury marker CK-MB(P<0.05).Treatment with L-carnitine significantly improved myocardial function,restored blood pressure in septic mice,and increased their survival rate from 12.50%to 81.25%(P<0.05).Compared with the Sham group,the contractile function and calcium transients of acutely isolated single cardiomyocytes were significantly reduced in the Sepsis group(P<0.05),while L-carnitine treatment remarkably restored the contractile function and calcium release capacity of septic cardiomyocytes(P<0.05).Both in vivo and in vitro experiments showed that TG and FFA levels were significantly increased(P<0.05),and ATP levels was significantly decreased(P<0.05)in the Sepsis and LPS groups—effects significantly reversed by L-carnitine treatment.Compared with the CTRL group,the basal oxidation rate and maximum oxidation capacity of fatty acids in cardiomyocytes of the LPS group were significantly reduced(P<0.05),and L-carnitine treatment notably improved these indicators.Compared with the CTRL group,the expression and activity of CPT1A in cardiomyocytes of the LPS group were significantly decreased(P<0.05),while L-carnitine treatment significantly increased the expression and activity of CPT1A(P<0.05).In LPS group cardiomyocytes,green fluorescently labeled palmitic acid primarily formed numerous granular/clumpy aggregates in the cytoplasm with minimal mitochondrial colocalization.In the L-carnitine group,the green fluorescent granules in the cytoplasm of cardiomyocytes were smaller,and colocalization with mitochondria was increased.However,the L-carnitine+Eto group exhibited similar phenomena to the LPS group.In addition,both in vivo and in vitro experiments demonstrated that treatment with the CPT1A inhibitor Eto reversed the effect of L-carnitine.Compared with the L-carnitine group,the ATP content in the L-carnitine+Eto group was significantly decreased(P<0.05),while the FFA content was significantly increased(P<0.05).Conclusion L-carnitine facilitates fatty acid entry into mitochondria for β-oxidation via a CPT1A-dependent mechanism,thereby ameliorating fatty acid oxidation dysfunction in septic cardiomyocytes and improving myocardial contractile function.

As a new hypoglycemic drug,Dapagliflozin has attracted much attention because of its unique hypoglycemic mechanism. It has been used in many studies on type 2 diabetes mellitus,but the application of type 1 diabetes mellitus(T1DM)in the eastern population is rare. This article uses Dapagliflozin through a case of obese T1DM to provide new ideas for the treatment of T1DM.

Objective:To develop a risk prediction lineogram of neooperative atrial fibrillation in patients with esophageal cancer.Methods:The clinical data of 1 509 patients undergoing esophageal cancer surgery admitted to the department of esophageal surgery of our hospital from December 2019 to April 2022 were gathered, and they were divided into two layers according to whether they had new atrial fibrillation after surgery. In each layer, they were randomly divided into training set and test set in a ratio of 7∶3. In the training population, the multi-factor logistic regression method was used to establish the prediction model, and the line graph of the prediction model was drawn. The ROC curve and calibration curve were drawn to assess the differentiation ability and calibration ability of the prediction model. The test set population is used to validate the prediction model. Results:A total of 1 509 patients with esophageal cancer were included in the study, and the incidence of new atrial fibrillation after surgery was 247 patients(16.4%). A total of 1 039 patients(68.9%) were enrolled in the training set. The multivariate logistic regression model indicated that age, gender, BMI, pulmonary infection, the use of invasive ventilator, and the need for additional drainage of fluid accumulation were the influencing factors for new postoperative atrial fibrillation. The AUC of the training set prediction model under ROC curve was 0.775(95% CI: 0.737-0.812, P<0.001), indicating that the model has high predictive discrimination ability. Calibration curve and Hosmer- Lemeshow test results P=0.796, indicating that the model has good consistency of prediction ability. There were 470 subjects(31.1%) in the test set. The results showed that the AUC of the prediction model under the ROC curve was 0.773(95% CI: 0.719-0.826, P<0.001), indicating that the prediction model still has a high discriminative ability in the test set population. Conclusion:Patients with age, gender, BMI, pulmonary infection, the use of invasive ventilator, and the need for additional drainage of effusion are at higher risk of new atrial fibrillation after surgery. The timely prediction, prevention and management of POAF are crucial to improve the prognostic quality of postoperative patients with esophageal cancer by constructing clinical prediction models.

【Objective】 To explore the technical methods and clinical efficacy of transvaginal or transrectal repair in the treatment of iatrogenic bladder fistula. 【Methods】 The clinical data of 7 cases of iatrogenic bladder fistula patients treated during 2016 and 2019 were retrospectively analyzed, including 6 cases of vesicovaginal fistula (VVF) and 1 case of vesicorectal fistula (VRF). The operation was conducted 3 to 10 months after the diagnosis of urinary fistula, and the vagina or rectum was fully cleaned before operation. Modified Latzko technique was employed to separate the gap between the bladder wall and vaginal or rectal wall along the fistula, the fistula scar was sharply removed, and the fistula, bladder wall, vaginal or intestinal wall, and vaginal or intestinal mucosa were sutured in layers. The urinary catheter was indwelled for 4 weeks. 【Results】 All 7 cases were successfully repaired at one procedure. No urine leakage was found after the urinary catheter was removed. There was no recurrence after 6 to 12 months of follow-up. 【Conclusion】 Selective application of the modified Latzko technique to repair iatrogenic urinary fistula through the natural lumen is an advantageous treatment scheme, which simplifies the operation and reduces trauma.

Objective:To investigate the effect of exposure to histological chorioamnionitis(HCA) on premature infants with respiratory distress syndrome(RDS)complicated with bronchopulmonary dysplasia(BPD).Methods:The clinical data of premature infants with gestational age<32 weeks and survival>14 days who were born in the department of obstetrics and admitted into NICU at Qingdao Women and Children′s Hospital from January 2018 to December 2020 were collected.According to placental pathology, they were divided into positive HCA + positive RDS group(observation group)and negative HCA + positive RDS group(control group). T-test, rank sum test and χ2 test were used to analyze the occurrence and clinical characteristics of BPD between the two groups.For premature infants with positive HCA who were diagnosed as BPD, Spearman rank correlation was used to analyze the correlation between HCA stage and BPD severity. Results:There were a total of 162 premature infants with RDS.The average gestational age at birth was 29.29(28.29, 30.43) weeks, and the average birth weight was 1.32(1.13, 1.55)kg; the incidence of BPD was 69.8%(113/162), and the mortality rate of BPD was 2.7%(3/113). There were 114 cases in the observation group and 48 cases in the control group.The incidence of BPD in the observation group was 76.3%(87/114), which was higher than that in the control group(54.2%, 26/48), and the difference was statistically significant( P<0.05). Further study of 87 premature infants with positive HCA who were diagnosed as BPD showed that, the correlation between the stage of HCA and the severity of BPD had not been confirmed( rs=0.062, P=0.571). Serum C-reactive protein before the mother used antibiotics and procalcitonin on the first day after birth in the observation group were higher than those in the control group, and the differences were statistically significant( P<0.05). Among 113 premature infants with RDS who were diagnosed as BPD, the time of antibiotic use, length of stay in intensive care unit and hospitalization cost in positive HCA group were higher than those in negative HCA group, and the differences were statistically significant( P<0.05). Conclusion:HCA exposure will increase the risk of BPD in premature infants with RDS.In addition, HCA also increases the intake period of antibiotics, length of stay and cost of intensive care unit in premature infants with BPD.

Objective:To investigate the correlation between histologic chorioamnionitis(HCA) and periventricular leukomalacia(PVL) in preterm infants less than 34 weeks old.Methods:A total of 287 preterm infants born in Qingdao Women′s and Children′s Hospital from January 2018 to December 2018, whose mothers underwent placental pathological examination and preterm infants transferred to the neonatal intensive care unit for treatment, and whose gestational age was less than 34 weeks old, were selected as the study objects. According to the results of placental pathological examination, the infants were divided into two groups: the positive HCA group(167 cases)and the negative HCA group(120 cases). The incidence of PVL was compared between the two groups. According to the results of placental pathological examination and the stage standard of HCA, the preterm infants who had been diagnosed with PVL(41 cases) were divided into three groups: the non-HCA group, the early HCA group and the middle/late HCA group.The severity of PVL, clinical data, complications were compared in each groups, and the conditions that following up to 6 months were adjusted.Results:PVL was 19.16%(32/167) in the positive HCA group and was 7.50%(9/120) in the negative HCA group.There was significant difference in the incidence of PVL between the two groups( P<0.05). Among the preterm infants with PVL, 21.95%(9/41) was in non-HCA group, 31.71%(13/41) was in the early HCA group, and 46.34%(19/41) was in the middle/late HCA group.The severity of PVL, 1 min Apgar score, white blood cell count at 24 h after birth, the incidence of bronchopulmonary dysplasia, the number of hospital stay, the use of antibiotics, the mental development index(MDI) and psychomotor development index(PDI) at the adjusted gestational age to 6 months were significant differences among the three groups( P<0.05). Moreover, the degree of HCA inflammation was positively correlated with the severity of PVL( r s=0.374, P=0.016). Conclusion:There is a correlation between HCA and PVL in premature less than 34 weeks old.With the increasing of HCA inflammation, the incidence and severity of PVL increase. With the progression of the severity of inflammation, the white blood cell count at 24 h after birth, the incidence of bronchopulmonary dysplasia, the use of antibiotics and the time of hospital stay increase, the MDI and PDI scores at the adjusted gestational age to 6 months decrease.

Objective:To investigate the best neutralization ratio of protamine and heparin during off-pump coronary artery bypass grafting(OPCABG) by analyzing the advantages and disadvantages of heparin residue after OPCABG.Methods:From July 2018 to January 2019, 112 patients undergoing elective OPCABG were included in this study. The patients’ whole blood was drawn at 2 time points, including before entering operating room and entering intensive care unit, to receive thrombelastography(TEG) and heparinase-modified thromboelastography(hmTEG) . Conventional coagulation indexes such as activated coagulation time(ACT) were also detected. All the patients were divided into 3 groups, the non-heparin residue group(30 cases), heparin residue group 1(42 cases) and heparin residue group 2(40 cases) according to the laboratory results of TEG, hmTEG and ACT. We observed the dosage of each group of protamine and heparin, as well as the ratio of heparin and protamine. The changes of R time in TEG and ACT between 3 groups were analyzed and compared. Postoperative chest tube drainage at postoperative 12 h and 48 h, cTnI peak value, incidence of perioperative myocardial infarction(MI), incidence of reoperation and poor wound healing, amount of blood loss and transfusion, and acute renal injury were compared between the 3 groups.Results:No significant trio-group differences existed in basic clinical characteristics(all P>0.05). Postoperative R(CKH)time was similar in the 3 groups( P>0.05). Comparing with heparin residue group 1 and heparin residue group 2, the ACT after protamine neutralizing heparin and postoperative R time were decreased, the dosage of protamine, ratio of heparin and protamine, cTnI peak value were increased in the non-heparin residue group( P<0.05). Comparing with heparin residue group 2, the dosage of heparin, postoperative chest tube drainage at postoperative 12h and 48h, amount of blood transfusion and transfusion probability were significantly decreased in non-heparin residue group( P<0.05), but compared with group 1 of heparin residue, there was no significant difference in the above indexes( P>0.05). The perioperative myocardial infarction, incidence of reoperation and poor wound healing, postoperative acute renal injury and time of in ICU stay showed no significant differences between the 3 groups( P>0.05). Conclusion:Moderate heparin residue after OPCAB suggests that it has myocardial protective effect, and does not significantly increase the risk of bleeding. A large number of heparin residues can affect the coagulation function and lead to bleeding tendency, increase the amount of blood loss and transfusion. It is reasonable to make ACT after protamine neutralize heparin higher than the level of ACT before operation, and not higher than 20% of the level before operation.