ObjectiveTo establish preliminary diagnostic criteria for spleen and kidney deficiency syndrome in ischemic stroke patients and provide a basis for standardized diagnosis and treatment of ischemic stroke. MethodsRelevant literature on the diagnostic criteria for spleen and kidney deficiency syndrome in ischemic stroke patients was retrieved， and data were mined and extracted to form an item pool. Based on the formation of the item pool， this study used the Delphi method to initiate two rounds of questionnaire surveys with selected experts to complete the initial screening of items and the discrimination of symptom importance. A prospective clinical investigation method was adopted to collect clinical information from patients， and statistical analysis methods and data mining techniques were comprehensively used to determine their primary and secondary symptoms. Based on the clear main and secondary symptoms identified， combined with expert group discussions， the study established preliminary diagnostic criteria for spleen and kidney deficiency syndrome in ischemic stroke patients. ResultsA total of 25 relevant syndrome differentiation standards were included. After splitting， standardizing， and screening the items， the study established a pool of 48 items. The first round of questionnaire survey consulted 30 experts， with both the positive coefficient of experts and the effectiveness rate of the questionnaire reaching 100%. The Kendall's coefficient of concordance was 0.359. According to the item screening criteria， 26 items were retained in this round of questionnaire survey. A total of 176 cases were collected through clinical information investigation， including 94 cases with spleen and kidney deficiency syndrome and 82 cases without spleen and kidney deficiency syndrome. The statistical results were as follows： ① Descriptive statistics： The main symptoms with a frequency of ≥ 30% included mental fatigue and lack of strength， weakness of the lower back and knees， etc. The secondary symptoms with a frequency of ≥ 10% and ≤ 30% were lassitude and disinclination to talk， shortness of breath， etc. ② Binary logistic regression analysis： The main symptoms with an odds ratio （OR） value of ≥ 3 were mental fatigue and lack of strength， weakness of the lower back and knees， etc. The secondary symptoms with an OR value of ≥ 1 and ≤ 3 were lassitude and disinclination to talk， shortness of breath， etc. Artificial neural network： The main symptoms with a weight value（W_ij）of ≥ 0.5 and < 1 were mental fatigue and lack of strength， lassitude and disinclination to talk， etc. The secondary symptoms with W_ij of ≥ 0.3 and < 0.5 were shortness of breath， flaccid limbs， etc. In the second round of questionnaire survey， a total of 37 experts were consulted， with both the positive coefficient of experts and the effectiveness rate of the questionnaire reaching 100%. The Kendall's coefficient of concordance was 0.237. According to the criteria to determine primary and secondary symptoms based on the Delphi method， the main symptoms included in this round of the questionnaire were mental fatigue and lack of strength， lassitude and disinclination to talk， etc.， and the secondary symptoms were shortness of breath， dizziness， etc. ConclusionThe main symptoms of spleen and kidney deficiency syndrome in ischemic stroke patients are mental fatigue and lack of strength， weakness of the lower back and knees， loose stool， pale and edematous tongue texture possibly with tooth marks， and deep and thready pulse or weak pulse. The secondary symptoms include shortness of breath， dizziness， tinnitus and deafness， decreased appetite or postprandial abdominal distension， pale complexion， frequent micturition at night， dull tongue texture， and white and slippery tongue coating. The preliminarily established diagnostic criteria for spleen and kidney deficiency syndrome in ischemic stroke patients can provide a standardized and objective basis， thereby better guiding clinical diagnosis and treatment of ischemic stroke.

BACKGROUND:In the initial stage of multiple sclerosis,central immune cells activate and release a large number of inflammatory factors,causing white matter demyelination and even involving gray matter neurons.The equilibrium of differentiation between different subsets of CD4+ T cells plays an important role in the progression of experimental autoimmune encephalomyelitis.The previous results of the research group showed that the active ingredient astragalus glycoprotein in astragalus can regulate the immune response in experimental autoimmune encephalomyelitis mice,and whether it has a regulatory effect on the differentiation of T cell subsets has not been determined. OBJECTIVE:To explore the therapeutic effects and immune regulatory mechanisms of astragaloside IV on experimental autoimmune encephalomyelitis mice. METHODS:Female C57BL/6 mice were divided into the normal control group,experimental autoimmune encephalomyelitis disease model group,and astragaloside IV treatment group(n=8 per group).Myelin oligodendrocyte glycoprotein peptides 35-55 were used for experimental autoimmune encephalomyelitis model induction in the last two groups.On day 10 to 28 after immunization,the astragaloside IV treatment group was treated with 40 mg/kg per day astragaloside IV intragastrically.Body weight and clinical scores of mice in each group were recorded from the immunization day to the 28th day.On the 28th day after immunization,the mouse spinal cord was taken and made into frozen sections for hematoxylin-eosin staining and Lux fast blue staining to observe pathological changes in the spinal cord.Percentage of splenic T cell subsets was detected using flow cytometry.Western blot assay was used to determine the protein expression of interferon-γ,interleukin-17 and interleukin-6 in the spinal cord.Levels of interferon-γ,interleukin-17,interleukin-6 and interleukin-4 in supernatants of cultured splenocytes were determined by ELISA. RESULTS AND CONCLUSION:(1)Compared with the experimental autoimmune encephalomyelitis disease model group,astragaloside IV could reduce the degree of weight loss in experimental autoimmune encephalomyelitis mice(P<0.05),ameliorate clinical symptoms(P<0.05),inhibit the infiltration of inflammatory cells and alleviate myelin loss(P<0.01,P<0.05).(2)Compared with the experimental autoimmune encephalomyelitis disease model group,astragaloside IV could inhibit the proportion of CD4+T cell subsets expressing interferon-γ(P<0.001)and interleukin-17(P<0.001),but increase percentages of CD4+ interleukin-10+(P<0.001)and CD4+ transforming growth factor-β+(P<0.01)T cell subsets.(3)Astragaloside IV could inhibit the expression of interferon-γ(P<0.05,P<0.01),interleukin-17(P<0.05,P<0.05),and interleukin-6(P<0.05,P<0.05)in the spinal cord and spleen,and up-regulate the expression of interleukin-4(P<0.01)in spleen.(4)These findings confirm that astragaloside IV alleviates clinical symptoms in experimental autoimmune encephalomyelitis mice,which may be related to regulating the splenic T cell subsets,therefore,inhibiting the infiltration of inflammatory cells into the center and reducing the demyelination.

Objective:To evaluate the safety of early enteral nutrition (EEN) support in patients with severe intra-abdominal infection and intestinal fistulas.Methods:This was a retrospective cohort study. We collected relevant clinical data of 204 patients with severe intra-abdominal infection and intestinal fistulas who had been managed in the No. 1 Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University between 1 January 2017 and 1 January 2020. The patients were allocated to EEN or delayed enteral nutrition (DEN) groups depending on whether enteral nutrition had been instituted within 48 hours of admission to the intensive care unit. The primary outcome was 180-day mortality. Other outcomes included rates of intraperitoneal hemorrhage, septic shock, open abdominal cavity, bloodstream infection, mechanical ventilation, and continuous renal replacement therapy. Risk factors for mortality were analyzed by logistic regression.Results:There were no significant differences in hematological data or other baseline characteristics between the two groups at the time of admission to the intensive care unit (all P>0.05). However, septic shock (31.2% [15/48] vs. 15.4% [24/156], χ 2=4.99, P=0.025), continuous renal replacement therapy (27.1% [13/48] versus 9.0% [14/156], χ 2=8.96, P=0.003), and 180-day mortality (31.2% [15/48] vs. 7.7% [12/156], χ 2=15.75, P<0.001) were significantly more frequent in the EEN than the DEN group (all P<0.05). Multivariate regression analysis showed that older age (OR=1.082, 95%CI:1.027-1.139, P=0.003), worse Acute Physiology and Chronic Health Evaluation (APACHE) II scores (OR=1.189, 95%CI: 1.037-1.363, P=0.013), higher C-reactive protein (OR=1.013, 95%CI:1.004-1.023, P=0.007) and EEN (OR=8.844, 95%CI:1.809- 43.240, P=0.007) were independent risk factors for death in patients with severe intra-abdominal infection and intestinal fistulas. Conclusion:EEN may lead to adverse events and increase mortality in patients with both enterocutaneous fistulas and severe abdominal infection. EEN should be implemented with caution in such patients.

Objective:To investigate mechanisms of IL-17D on cytotoxic function of CD93+CTL in lung tumor microenviron-ment(TME)and promotion of Platycodon grandiflorum(PG).Methods:Lung of B16 melanoma model mice and control mice were treated with PG or IL-17D,and lung tumor clone formation was observed.IL-17D expression change in lung was detected by single cell sequencing,immunofluorescence staining and flow cytometry.Single cell sequencing and flow cytometry were used to detect CD93+CTL content,cytotoxic phenotype and functional factors changes,including CD107a,perforin,granzyme B,chemokine CCL2,CXCL9 and their ligand CCR2 and CXCR3.Western blot and RT-PCR were used to detect effect of Platycodonopsis saponin D on IL-17D and its transcriptional regulator NRF2 expressions in EL4 cells.Results:Pulmonary CD93+CTL highly expressed cytotoxic effectors such as perforin and CD107a and chemokine receptors CXCR3 and CCR2 than CD93-CTL,while there was no significant difference in secretion of granzyme B.In mouse lung tumor model,pulmonary IL-17D and CD93+CTL were significantly decreased(P<0.001);in tumor-bearing mice after IL-17D backfill assay,or after 10 days of treatment with PG,proportion and absolute number of IL-17D and CD93+CTL in lungs were significantly increased(P<0.05),and tumor clones were significantly reduced;meanwhile,tumor-local expressions of cytokines CCL2,CXCL9,which are related to recruitment and function of CD93+CTL,and IL-17D were significantly upregulated.Up-regulation of IL-17D and its transcriptional regulator NRF2 by PG was verified in vitro experiments on EL4 cell line by PD.Conclusion:Traditional Chinese medicine PG and its extracts can up-regulate expression of IL-17D in lungs,improve infiltration and cytotoxic function of CD93+CTL and antagonize malignant progression of lung tumors,this is an important phar-macological mechanism of PG in improving immune TME of tumors in lung.

Objective:To assess the association between body mass index (BMI) and major adverse cardiovascular and cerebrovascular events (MACCE) among patients with acute coronary syndrome (ACS).Methods:This was a multicenter prospective cohort study, which was based on the Improving Care for Cardiovascular Disease in China (CCC) project. The hospitalized patients with ACS aged between 18 and 80 years, registered in CCC project from November 1, 2014 to December 31, 2019 were included. The included patients were categorized into four groups based on their BMI at the time of admission: underweight (BMI<18.5 kg/m 2), normal weight (BMI between 18.5 and 24.9 kg/m 2), overweight (BMI between 25.0 and 29.9 kg/m 2), and obese (BMI≥30.0 kg/m 2). Multivariate logistic regression models was used to analyze the relationship between BMI and the risk of in-hospital MACCE. Results:A total of 71 681 ACS inpatients were included in the study. The age was (63.4±14.7) years, and 26.5% (18 979/71 681) were female. And the incidence of MACCE for the underweight, normal weight, overweight, and obese groups were 14.9% (322/2 154), 9.5% (3 997/41 960), 7.9% (1 908/24 140) and 7.0% (240/3 427), respectively ( P<0.001). Multivariate logistic regression analysis showed a higher incidence of MACCE in the underweight group compared to the normal weight group ( OR=1.30, 95% CI 1.13-1.49, P<0.001), while the overweight and obese groups exhibited no statistically significant difference in the incidence of MACCE compared to the normal weight group (both P>0.05). Conclusion:ACS patients with BMI below normal have a higher risk of in-hospital MACCE, suggesting that BMI may be an indicator for evaluating short-term prognosis in ACS patients.

Objective:To evaluate the safety of early enteral nutrition (EEN) support in patients with severe intra-abdominal infection and intestinal fistulas.Methods:This was a retrospective cohort study. We collected relevant clinical data of 204 patients with severe intra-abdominal infection and intestinal fistulas who had been managed in the No. 1 Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University between 1 January 2017 and 1 January 2020. The patients were allocated to EEN or delayed enteral nutrition (DEN) groups depending on whether enteral nutrition had been instituted within 48 hours of admission to the intensive care unit. The primary outcome was 180-day mortality. Other outcomes included rates of intraperitoneal hemorrhage, septic shock, open abdominal cavity, bloodstream infection, mechanical ventilation, and continuous renal replacement therapy. Risk factors for mortality were analyzed by logistic regression.Results:There were no significant differences in hematological data or other baseline characteristics between the two groups at the time of admission to the intensive care unit (all P>0.05). However, septic shock (31.2% [15/48] vs. 15.4% [24/156], χ 2=4.99, P=0.025), continuous renal replacement therapy (27.1% [13/48] versus 9.0% [14/156], χ 2=8.96, P=0.003), and 180-day mortality (31.2% [15/48] vs. 7.7% [12/156], χ 2=15.75, P<0.001) were significantly more frequent in the EEN than the DEN group (all P<0.05). Multivariate regression analysis showed that older age (OR=1.082, 95%CI:1.027-1.139, P=0.003), worse Acute Physiology and Chronic Health Evaluation (APACHE) II scores (OR=1.189, 95%CI: 1.037-1.363, P=0.013), higher C-reactive protein (OR=1.013, 95%CI:1.004-1.023, P=0.007) and EEN (OR=8.844, 95%CI:1.809- 43.240, P=0.007) were independent risk factors for death in patients with severe intra-abdominal infection and intestinal fistulas. Conclusion:EEN may lead to adverse events and increase mortality in patients with both enterocutaneous fistulas and severe abdominal infection. EEN should be implemented with caution in such patients.

Objective:To explore the prognostic predictive value of deep neural network (DNN) assisted myocardial contrast echocardiography (MCE) quantitative analysis of ST-elevated myocardial infarction (STEMI) patients after successful percutaneous coronary intervention(PCI).Methods:A retrospective analysis was performed in 97 STEMI patients with thrombolysis in myocardial infarction-3 flow in infarct vessel after primary PCI in Renmin Hospital of Wuhan University from June to November 2021. MCE was performed within 48 h after PCI. Patients were followed up to 120 days. The adverse events were defined as cardiac death, hospitalization for congestive heart failure, reinfarction, stroke and recurrent angina. The framework consisted of the U-net and hierarchical convolutional LSTMs. The plateau myocardial contrast intensity (A), micro-bubble rate constant (β), and microvascular blood flow (MBF) for all myocardial segments were obtained by the framework, and then underwent variability analysis. Patients were divided into low MBF group and high MBF group based on MBF values, the baseline characteristics and adverse events were compared between the two groups. Other variables included biomarkers, ventricular wall motion analysis, MCE qualitative analysis, and left ventricular ejection fraction. The relationship between various variables and prognosis was investigated using Cox regression analysis. The ROC curve was plotted to evaluate the diagnostic efficacy of the models, and the diagnostic efficacy of the models was compared using the integrated discrimination improvement index (IDI).Results:The time-cost for processing all 3 810 frames from 97 patients was 377 s. 92.89% and 7.11% of the frames were evaluated by an experienced echocardiographer as "good segmentation" and "correction needed". The correlation coefficients of A, β, and MBF ranged from 0.97 to 0.99 for intra-observer and inter-observer variability. During follow-up, 20 patients met the adverse events. Multivariate Cox regression analysis showed that for each increase of 1 IU/s in MBF of the infarct-related artery territory, the risk of adverse events decreased by 6% ( HR 0.94, 95% CI =0.91-0.98). There was a 4.5-fold increased risk of adverse events in the low MBF group ( HR 5.50, 95% CI=1.55-19.49). After incorporating DNN-assisted MCE quantitative analysis into qualitative analysis, the IDI for prognostic prediction was 15% (AUC 0.86, sensitivity 0.78, specificity 0.73). Conclusions:MBF of the area supplied by infarct-related artery after STEMI-PCI is an independent protective factor for short-term prognosis. The DNN-assisted MCE quantitative analysis is an objective, efficient, and reproducible method to evaluate microvascular perfusion. Assessment of culprit-MBF after PCI in STEMI patients adds independent short-term prognostic information over qualitative analysis.It has the potential to be a valuable tool for risk stratification and clinical follow-up.

OBJECTIVE：To establish a method for the determination of aloesin in plasma of rats ，and to investigate pharmacokinetic characteristics of aloesin. METHODS ：The plasma samples were precipitated with methanol. Using aloeresin D as internal standard ，the plasma concentration of aloesin was determined by LC-MS/MS. The determination was performed on Synergi Hydro-RP column with mobile phase consisted of 0.1‰ formic acid-methanol （gradient elution ）at the flow rate of 0.50 mL/min. The column temperature was 30 ℃，and sample size was 5 µL. The electrospray ionization source was applied to carry out negative ion detection with multiple reaction monitoring mode . The ion transitions for quantitative analysis were m/z 393.1→272.9（aloesin） and m/z 555.3→144.9（internal standard ），respectively. The concentration of aloesin in venous blood was determined by above method at 0.083，0.167，0.333，0.667，1，1.5，2.5，4，6，8，10 h after intravenous injection （3.35 mg/kg）and intragastric administration（16.75 mg/kg）of aloesin. DAS 3.0 software was used to calculate pharmacokinetic parameters. RESULTS ：The linear range of aloesin were 1-600 ng/mL（r＝0.994 5）. The lower limit of quantification was 1 ng/mL，and RSDs of within and between batches were less than 15％；accuracies within and between batches were within ±15％. The matrix factors were （92.74± 4.33）％-（94.84±2.57）％，and extraction recoveries were （69.04±2.13）％-（75.03±2.84）％；the deviation between the measured results of the stability test and the theoretical values were within ±15％. After intravenous injection and intragastric administration of aloesin ，main pharmacokinetic parameters were as follows ：cmax were（10 693.3±2 745.3）and（223.3±36.2）ng/mL；t1/2 were （2.45±1.45）and（3.33±1.91）h；AUC0－24h were（4 190.6±883.6）and（1 210.1±93.9）ng·h/mL（n＝3）. Absolute bioavailabi- lity was 11.13％. CONCLUSIONS ：The established method is rapid and sensitive for plasma determination of aloesin ，and suitable for its pharmacokinetic study.

OBJECTIVETo systematically review the safety of application of enhanced recovery after surgery(ERAS) to laparoscopic bariatric surgery.

METHODSThe randomized controlled trials (RCTs) or case-controlled trials concerning application of ERAS principles in bariatric surgery were collected by searching several national and international online databases, including PubMed, Cochrane Library, CNKI, EMBASE and Wanfang databases. Data collection was completed in October 2016. The ERAS protocol covered three phases (preoperative, intraoperative, and postoperative), including preoperative counseling, reduced fasting, early ambulation, early oral feeding, etc. The endpoints included at least one of the following parameters: length of stay (LOS), operation time, readmission rate within 30 days, morbidity of postoperative complication (major/minor), and reoperation rate within 30 days. The quality of enrolled literatures was evaluated according to Cochrane Handbook and Newcastle-Ottawa Scale. RevMan 5.2 software was applied to perform meta analysis. The weighted mean difference (WMD) was used to combine the statistics for the measurement data, and the ratio and its 95% confidence interval were used to combine the statistics for the counting data. Subgroup analysis was conducted based on the quality of the enrolled literatures for the results of high heterogeneity.

RESULTSA total of 7 studies, including 1 randomized controlled trail and 6 case-control studies, with 3264 patients were enrolled. Among the 3264 patients, 2051 received ERAS management (ERAS group) and 1213 received traditional perioperative management (control group). Meta analysis showed that compared with control group, ERAS group had shorter operative time (WMD=-17.56, 95%CI: -29.50 to -5.62, P=0.00), shorter length of hospital stay (WMD=-1.11, 95%CI: -1.31 to -0.92,P=0.00). There were no statistically significant differences between the two groups in the morbidity of postoperative major complication(OR=1.21, 95%CI:0.87 to 1.69, P=0.26) or minor complication (OR=1.25, 95%CI:0.99 to 1.58, P=0.06), re-admission rate within 30 days (OR=1.07, 95%CI: 0.81 to 1.43, P=0.63) and re-operation rate within 30 days(OR=1.33, 95%CI: 0.84 to 2.11, P=0.23).

CONCLUSIONApplication of ERAS protocols to bariatric surgery is safe and feasible, which can also reduce length of hospital stay and operative time, and accelerate recovery.

Spinal cord stimulation (SCS) is a promising technique for treating disorders of consciousness (DOCs). However, differences in the spatio-temporal responsiveness of the brain under varied SCS parameters remain unclear. In this pilot study, functional near-infrared spectroscopy was used to measure the hemodynamic responses of 10 DOC patients to different SCS frequencies (5 Hz, 10 Hz, 50 Hz, 70 Hz, and 100 Hz). In the prefrontal cortex, a key area in consciousness circuits, we found significantly increased hemodynamic responses at 70 Hz and 100 Hz, and significantly different hemodynamic responses between 50 Hz and 70 Hz/100 Hz. In addition, the functional connectivity between prefrontal and occipital areas was significantly improved with SCS at 70 Hz. These results demonstrated that SCS modulates the hemodynamic responses and long-range connectivity in a frequency-specific manner (with 70 Hz apparently better), perhaps by improving the cerebral blood volume and information transmission through the reticular formation-thalamus-cortex pathway.
Adolescent ; Adult ; Brain ; physiopathology ; Consciousness ; physiology ; Consciousness Disorders ; physiopathology ; therapy ; Female ; Hemodynamics ; physiology ; Humans ; Male ; Middle Aged ; Pilot Projects ; Spinal Cord ; physiopathology ; surgery ; Spinal Cord Stimulation ; methods ; Young Adult