ObjectiveTo explore the possible mechanisms of Shujin Jiannao Formula （舒筋健脑方） for cerebral palsy. MethodsThirty 7-day-old SD rats were randomly divided into normal group， model group， and Shujin Jiannao Formula group， with 10 rats in each group. The model group and Shujin Jiannao Formula group established a cerebral palsy model by the classic Rice-Vannucci method. After successful modeling， rats in Shujin Jiannao Formula group were given Shujin Jiannao Formula 16 g/（kg·d） by gavage， while the normal group and model group were given normal saline 10 ml/（kg·d） by gavage once a day. After one week of intervention， the rats' body weight was measured， and Zea-Longa scores， the righting reflex test， and the hindlimb suspension test were conducted for assessment； hematoxylin-eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissue， and the number of Nissl-positive neurons was counted； enzyme-linked immunosorbent assay （ELISA） was employed to measure levels of inflammatory cytokines in the brain tissue， specifically interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）； immunofluorescence was used to detect the expression levels of neurofilament protein 200 （NF200） and myelin basic protein （MBP） in brain tissue； Western Blot analysis was conducted to determine the protein levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt/PKB/Rac）， and mammalian target of rapamycin （mTOR） in brain tissue. ResultsCompared with the normal group， rats in the model group showed significantly higher Zea-Longa scores and lower scores in the hindlimb suspension test （P＜0.01）； pathological findings revealed loose structure in the cerebral cortex， hippocampal atrophy， and neuronal damage in brain tissue. Levels of IL-1β and TNF-α elevated， and the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region reduced， and immunofluorescence intensity of NF200 and MBP， as well as protein expression levels of PI3K and mTOR， significantly decreased （P＜0.05 or P＜0.01）. Compared with the model group， rats in Shujin Jiannao Formula group showed decreased Zea-Longa scores and increased hindlimb suspension test scores （P＜0.05）； pathological damage in brain tissue alleviated， levels of IL-1β and TNF-α reduced， the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region increased， and the immunofluorescence intensity of NF200 and MBP， as well as the protein levels of PI3K and mTOR， significantly elevated （P＜0.05 or P＜0.01）. There were no statistically significant differences among the groups in body weight， body-turning time， or AKT protein levels in brain tissue （P＞0.05）. ConclusionShujin Jiannao Formula can improve the neurological function of rats with cerebral palsy， exert neurorestorative effects， and its mechanism of action may be related to the reduction of inflammatory response in brain tissue and the activation of the PI3K/AKT/mTOR signaling pathway.

OBJECTIVE To evaluate the inhalation safety of domestic pharmaceutical metered-dose inhalers accessories hydrofluoroalkane(HFA)-134a. METHODS The 21 d repeat dose inhalation toxicity study and Hartley guinea pig active systemic anaphylaxis for samples from two major domestic manufacturers were tested. RESULTS SD rats were exposed nose-only separately to the samples from two major domestic manufacturers at the concentration of (2 140±58)g·m–3 and (2 129±59)g·m–3 respectively for 21 consecutive days(2 h each day), there were statistically significant differences in the following indicators: some indicators of hematology such as neutrophil count, basophil, basophil ratio, monocyte ratio, hematocrit and platelet count, some indicators of blood biochemistry such as albumin content, total bilirubin content, chloride ion and potassium ion, some indicators of urine such as nitrite, leukocytes, urobilinogen, protein and bilirubin, organ weight and coefficients of kidney, thymus, heart, pituitary and lung. No systemic sensitization reaction were observed in guinea pigs. CONCLUSION The domestic pharmaceutical HFA-134a have certain toxic effects on some organs, blood and urine biochemical indicators of SD rats exposed to 250 times of the clinical maximum dose for continuously 21 d, however, further research is need to access whether inhalation is safe in normal clinical dose.

Objective There are 6 leads of limb lead ECG,and the cardiac electrical axis can be estimated by any combination of two leads.In this paper,the estimation accuracy of all 15 pairs of limb-lead combinations was compared.Methods Using the open database of 12-lead electrocardiograms(at a sampling frequency of 500 Hz with duration of 10 seconds during resting state)from PhysioNet,totally 21 306 ECG records were extracted with age≥18 years which labeled as single sinus type(axis normal),including 6 153 records with Sinus Rhythm,10 916 records with Sinus Bradycardia,3 466 records with Sinus Tachycardia,and 771 records with Sinus Irregularity.Moreover,totally 2 323 axis deflection recordings with age≥18 years were extracted,including 1 526 records with Axis left shift,and 797 records with Axis right shift.Cardiac electrical axis was estimated with the net amplitude(or area)of QRS complex(algebraic sum of positive and negative amplitude or area)by any pair of leads from{Ⅰ,Ⅱ},{Ⅰ,Ⅲ},{Ⅰ,aVR},{Ⅰ,aVL},{Ⅰ,aVF},{Ⅱ,Ⅲ},{Ⅱ,aVR},{Ⅱ,aVL},{Ⅱ,aVF},{Ⅲ,aVR},{Ⅲ,aVL},{Ⅲ,aVF},{aVR,aVL},{aVR,aVF},{aVL,aVF},respectively.Results For the amplitude-based method,the recognition accuracy for the normal,left and right axes from{Ⅰ,Ⅱ}and{Ⅱ,aVL}is 93.56%and 93.50%,respectively,which is better than that of the traditional classical method{I,aVF}(92.93%).For the area-based method,the recognition accuracy from{Ⅲ,aVR},{Ⅰ,aVR},{Ⅰ,Ⅱ},{aVR,aVF},{Ⅱ,aVL}and{Ⅱ Ⅲ}is 92.66%,92.53%,92.29%,92.19%,92.10%and 91.91%,respectively,which is better than the traditional classical method{Ⅰ,aVF}(91.82%).Conclusion The accuracy of amplitude-based method is higher than that of area-based method.Lead pair{Ⅰ,Ⅱ}and{Ⅱ,aVL}have higher accuracy than traditional classical{Ⅰ,aVF}in automatic estimation of cardiac electrical axis for both amplitude and area method.

Objective To investigate the effect of ultrasound-guided erector spinae plane block(ESPB)on early postoperative respiratory function and inflammatory cytokines in patients with multiple rib fractures(MRFs).Methods Fifty-eight patients who underwent MRFs surgery,42 males and 16 females,aged 18-64 years,BMI 18.5-30.0 kg/m2,ASA physical status Ⅰ or Ⅱ,were selected from February 2019 to December 2021.The patients were divided into two groups using random number method:ESPB combined with general anesthesia group(group E)and general anesthesia alone group(group G),29 pa-tients in each group.All the patients in group E underwent ultrasound-guided ESPB in the lateral decubitus position after general anesthesia induction,and 0.5％ropivacaine 0.4 ml/kg was administered.Forced vital capacity(FVC),arterial blood gas analysis,VAS pain scores at rest and cough were recorded before anes-thesia induction,at discharge from PACU,24 and 48 hours after operation.The number of effective PCIA compressions during 0-24 hours and 24-48 hours after surgery and the number of rescue analgesia were re-corded.The concentrations of IL-6 and TNF-α were recorded before anesthesia induction,24 and 48 hours after operation.Results Compared with group G,the FVC was significantly higher,and the VAS score and PaCO2 were significantly lower in group E at discharge from PACU,24 and 48 hours after operation(P＜0.05).The number of effective PCIA compressions during 0-24 hours and 24-48 hours after surgery,the rate of rescue analgesia,the concentrations of IL-6 and TNF-α 24 and 48 hours after operation in group E were significantly lower than those in group G(P＜0.05).Conclusion Ultrasound-guided ESPB can pro-vide good postoperative analgesia,promote early postoperative recovery of respiratory function in patients with MRFs.

Patients with traumatic brain injury (TBI) may develop neurological complications such as Alzheimer′s disease, stroke and epilepsy, which severely affect their quality of life. Currently, neurological complications after TBI are poorly understood and there are no comprehensive treatments or definitive interventions for them. Complex pathophysiological changes in the brain, systemic immunological responses, and gastrointestinal dysfunction after TBI all severely affect the biodiversity of the intestinal microbiota and related metabolites, which leads to intestinal dysbiosis and metabolic disorders and exert continued effects on the nervous system. Intestinal microbial probiotic flora that colonize in living organisms are a category of active microorganisms beneficial to the host and supplementation of intestinal probiotics can have a modulatory effect on the nervous system directly or indirectly. The targeted therapeutic effects of intestinal microbial probiotic flora on neurological complications after TBI and the intrinsic mechanism of the effects have not been comprehensively summarized currently. For this purpose, the authors reviewed the research progress on the effects of regulating intestinal microbial probiotic flora on post-TBI neurological complications so as to provide a reference for the clinical prevention and treatment of post-TBI neurological complications.

AIM:To evaluate the efficacy,safety,and economy of camrelizumab(CAM)combined with platinum-containing chemotherapy(CT)for the first-line treatment of locally advanced/meta-static non-small cell lung cancer(NSCLC).METH-ODS:Chinese and English databases such as Pubmed,the Cochrane Library,China Knowledge Network,Wanfang Data,and other related web-sites were systematically searched.After literature screening,quality assessment,and data extraction of the literature according to the inclusion and ex-clusion criteria,two researchers conducted a rapid health technology assessment(HTA).RESULTS:A total of 7 systematic evaluations/Meta-analyses and 17 economics evaluations were included.In terms of effectiveness,compared to docetaxel che-motherapy,CAM+CT significantly prolonged the overall survival(OS),progression-free survival(PFS),and improved the objective remission rate(ORR)of mutation-negative patients with locally ad-vanced/metastatic NSCLC.Compared with CT and pembrolizumab(PEM),CAM+CT significantly pro-longed the PFS,and improved the ORR of mutation-negative patients with locally advanced/metastatic NSCLC.Subgroup analysis showed that CAM+CT significantly prolonged PFS in patients with PD-L1 ≥1％and PD-L1 ≥ 50％compared with CT.Compared with CT,CAM+CT significantly prolonged the OS and PFS of mutation-negative patients with locally advanced/metastatic squamous NSCLC.Compared with sintilimab(SIN),CAM+CT significantly pro-longed the PFS of mutation-negative patients with locally advanced/metastatic squamous NSCLC.Sub-group analysis showed that CAM+CT significantly prolonged OS in patients with PD-L1＜1％com-pared with CT.In terms of safety,CAM+CT was comparable in terms of the occurrence of all grades of adverse events,but the incidence of grade 3 or higher treatment-related adverse events was significantly increased compared with CT and PEM for mutation-negative locally advanced/meta-static NSCLC patients.CAM+CT was significantly in-creased the occurrence of all grades of adverse events compared with CT,but was comparable in terms of the occurrence of grade 3 or higher treat-ment-related adverse events.In terms of economy,CAM+CT has a cost-effectiveness advantage over CT for patients with mutation-negative advanced/metastatic squamous NSCLC.CAM+CT has a cost-effectiveness advantage over CT and PEM+CT;and CAM+CT does not have a cost-effectiveness ad-vantage over SIN+CT for patients with mutation-negative locally advanced/metastatic non-squa-mous NSCLC.CONCLUSION:CAM+CT has good ef-ficacy and cost-effectiveness for the first-line treat-ment of locally advanced/metastatic NSCLC,and the safety aspect is compared with CT,PEM or slightly worse.

Objective To explore the impact of adipokine metabolism on coronary microvascular dysfunction(MVD)and the clinical application value of Shexiang Tongxin dropping pill(STDP).Methods From Sep.2018 to Dec.2019,41 patients with coronary heart disease in Department of Cardiology,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled and divided into non-MVD group(20 cases)and MVD group(21 cases);29 MVD patients were randomly divided into basic treatment group(14 cases)and STDP group(15 cases)with basic treatment or additional STDP treatment for 3 months;and the patient's complaints,blood biochemical indicators,expression levels of plasma inflammatory factors and adipokines were analyzed.A myocardial ischemia-reperfusion model was established in male C57BL/6 mice aged 12-14 weeks.Mice were divided into sham operation group,ischemia-reperfusion(IR)group(normal saline gavage),and IR+STDP group(STDP gavage),with 5 mice in each group.The levels of plasma inflammatory factors were measured by enzyme-linked immunosorbent assay,the microvascular occlusion of the heart tissue was measured by thioflavin-S staining,and the differential expression proteins between the IR group and IR+STDP group were explored by proteomics analysis and verified by Western blotting.Results Compared with the non-MVD group,the MVD group showed a significant increase in plasma leptin level([9.89±2.42]μg/L vs[4.76±1.02]μg/L,P＜0.01),a significant decrease in adiponectin level([5.02±1.3]pg/mL vs[7.19±1.76]pg/mL,P＜0.05),and a significant increase in resistin level([9.20±2.03]μg/L vs[5.70±1.32]μg/L,P＜0.05).Pearson correlation analysis showed a positive correlation between leptin levels and MVD(r=0.82 and P＜0.01).Receiver operating characteristic curve analysis showed that the area under curve value of plasma leptin was 0.855(sensitivity 0.714,specificity 0.867,and optimal cutoff value＞9.395 μg/L).After 3 months of treatment,compared with the basic treatment group,the improvement rates of symptoms of chest distress and chest pain in the STDP group were significantly higher(73.3％[11/15]vs 21.4％[3/14]),and the levels of plasma leptin,interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were significantly lower([11.36±0.54]μg/L vs[12.12±0.85]μg/L,[3.96±1.76]pg/mL vs[8.65±1.29]pg/mL,[24.82±3.07]ng/mL vs[32.45±3.32]ng/mL,all P＜0.05).In animal studies,compared with the IR group,the mice in the IR+STDP group showed a 45％reduction in no-reflow area(P＜0.01)and a 23％reduction in low-reflow and no-reflow areas(P＜0.05)after myocardial ischemia-reperfusion;the expression levels of IL-6 and TNF-α were significantly decreased([378.25±19.66]pg/mL vs[457.32±32.01]pg/mL,[289.71±47.62]pg/mL vs[371.28±41.05]pg/mL,both P＜0.05).Proteomic analysis showed that the expression levels of von Willebrand factor(vWF)and intercellular cell adhesion molecule-1(ICAM-1)in the cardiac tissue of mice in the IR+STDP group were significantly lower than those in the IR group.Western blotting results also showed that the expression levels of vWF and ICAM-1 in the IR+STDP group were significantly lower than those in the IR group(both P＜0.01).Conclusion MVD patients have abnormal adipokine metabolism and high plasma leptin.STDP can improve clinical symptoms of MVD patients,reduce the plasma leptin level and inflammatory indicators,and the mechanism may be related to its antiplatelet and anti-inflammatory effects.

Objective:To summarize the clinical features,diagnosis and treatment of multisystem inflammatory syndrome in children (MIS-C) after novel coronavirus infection(COVID-19),so as to improve the early recognition of MIS-C.Methods:The general information,clinical manifestations,treatment and length of hospital stay of fifteen children diagnosed with MIS-C and hospitalized in the Department of Cardiology,Children's Hospital,Capital Institute of Pediatrics from December 1，2022 to January 31，2023 were retrospectively analyzed.Fifteen children were divided into shock group( n=6) and non-shock group( n=9) according to the criteria of shock,and the differences in general conditions and laboratory examinations before treatment were compared between two groups. Results:The mean age of fifteen children were (3.28±2.48) years (ranging from 9 months to 7.9 years),with a male to female ratio of 4:1.The mean time interval from COVID-19 to the onset of MIS-C was (30.60±9.91) days.The novel coronavirus vaccination rate was 7%.Fever,enlarged lymph nodes,cracked lips and a strawberry tongue were present in all children,with just one exhibiting peeling of the hands and feet.Compared with the non-shock group,patients in the shock group were older,the level of platelet decreased significantly,the level of procalcitonin,interleukin-10,N-terminal pro-brain natriuretic peptide(NT-proBNP) and ferritin significantly increased,the left ventricular ejection fraction and left ventricular fractional shortening decreased significantly,and the Z score of left ventricular end-systolic diameter significantly increased,and there were significant differences between two groups ( P<0.05).All 15 patients were treated with human intravenous immunoglobulin,and five patients with severe myocarditis and shock accepted combined high-dose methylprednisolone pulse therapy over a period of five days,with the doses gradually tapering off afterwards.The mean hospital stay of all patients was (11.00±4.80) days,while the mean shock correction time of six patients was (5.14±2.12) days.After six months of follow-up,15 patients showed excellent prognosis with coronary lesions recovered and without any new complications. Conclusion:Generally,MIS-C tends to occur 3-6 weeks after COVID-19,with more boys than girls.Older ones are more likely to suffer from shock.Focusing on NT-proBNP and cardiac function indicators could identify shock early.High-dose methylprednisolone pulse therapy may be effective and benefit for prognosis improvement in children complicated with both shock and severe myocarditis.

Cognitive dysfunction is one of the common central nervous systems (CNS) complications of diabetes mellitus, which seriously affects the quality of life of patients and results in a huge economic burden. The glymphatic system dysfunction mediated by aquaporin-4 (AQP4) loss or redistribution in perivascular astrocyte endfeet plays a crucial role in diabetes-induced cognitive impairment (DCI). However, the mechanism of AQP4 loss or redistribution in the diabetic states remains unclear. Accumulating evidence suggests that peripheral insulin resistance target tissues and CNS communication affect brain homeostasis and that exosomal miRNAs are key mediators. Glucose and lipid metabolism disorder is an important pathological feature of diabetes mellitus, and skeletal muscle, liver and adipose tissue are the key target insulin resistance organs. In this review, the changes in exosomal miRNAs induced by peripheral metabolism disorders in diabetes mellitus were systematically reviewed. We focused on exosomal miRNAs that could induce low AQP4 expression and redistribution in perivascular astrocyte endfeet, which could provide an interorgan communication pathway to illustrate the pathogenesis of DCI. Furthermore, the mechanisms of exosome secretion from peripheral insulin resistance target tissue and absorption to the CNS were summarized, which will be beneficial for proposing novel and feasible strategies to optimize DCI prevention and/or treatment in diabetic patients.

Ischemic stroke (IS) is a severe cerebrovascular disease with a high incidence, mortality, and disability rate. The first-line treatment for IS is the use of recombinant tissue plasminogen activator (r-tPA). Regrettably, numerous patients encounter delays in treatment due to the narrow therapeutic window and the associated risk of hemorrhage. Traditional Chinese medicine (TCM) has exhibited distinct advantages in preventing and treating IS. TCM enhances cerebral microcirculation, alleviates neurological disorders, regulates energy metabolism, mitigates inflammation, reduces oxidative stress injuries, and inhibits apoptosis, thereby mitigating brain damage and preventing IS recurrence. This article summarizes the etiology, pathogenesis, therapeutic strategies, and relationship with modern biology of IS from the perspective of TCM, describes the advantages of TCM in the treatment of IS, and further reviews the pharmacodynamic characteristics and advantages of TCM in the acute and recovery phases of IS as well as in post-stroke complications. Additionally, it offers valuable insights and references for the clinical application of TCM in IS prevention and treatment, as well as for the development of novel drugs.