Berberine (BBR) is the main pharmacological active ingredient of Coptidis, which has hypoglycemic effect, but its clinical application is limited due to its poor oral bioavailability. Polyphenols, derived from cinnamon, are beneficial for type 2 diabetes mellitus (T2DM). The combination of both may have an additive effect. The aim of this study was to investigate the hypoglycemic effect and mechanism of combined medication in diabetic rats. The modeling rats were randomly divided into 5 groups (berberine group, cinnamon group, combined group, metformin group, diabetic control group) and normal control group. The animal experiments were approved by the Animal Ethics Committee (approval number: HMUIRB2022003). The subjects were given orally, and the control group was given equal volume solvent and body weight was measured weekly. Thirty days after administration, oral glucose tolerance test and insulin sensitivity test were performed, and fasting blood glucose (FBG), glycated serum protein (GSP), and serum insulin (INS) levels were detected; high-throughput sequencing technology was used to detect intestinal microbiota structure; real-time quantitative PCR (RT-qPCR) and Western blot were used to detect G protein-coupled receptor 5 (TGR5) and glucagon-like peptide-1 (GLP-1) expression levels. The results showed that, compared with the diabetic control group, the levels of FBG (P < 0.01) and GSP (P < 0.01) in the combined group were lower, and the insulin resistance was improved, which was better than that in the berberine group. Combined treatment increased the relative abundance of Bacteroides, Prevotella and Lactobacillus, reversed the decrease in Lactobacillus in the berberine alone induction group, and the combination of the two could promote the expression of TGR5 and GLP-1. In summary, the combined application of cinnamon and berberine can regulate glucose metabolism better than the application of berberine alone. Berberine combined with cinnamon can improve the function of pancreatic islet β cells in diabetes mellitus type 2 rats by changing the intestinal microbiota, increasing the expression of TGR5 and GLP-1 proteins, and thereby better regulating glucose metabolism.

Objective To investigate the family aggregation of human hookworm infections in Sichuan Province and to identify its influencing factors, so as to provide insights into management of hookworm infections. Methods Three to four counties (districts) were sampled from basins, hilly regions and mountainous regions around the basins in Sichuan Province from 2017 to 2022 as fixed survey sites, and 17 to 30 counties (districts) were selected as mobile survey sites. At least 1 000 permanent residents at ages of 3 years and older were sampled from each survey site, and hookworm eggs were detected in human stool samples using the Kato-Katz technique. Subjects with 2 and more family members and at least 2 individuals diagnosed with hookworm infections in the county (district) where they lived were selected, and the familial aggregation of hookworm infections was analyzed using the test of goodness of fit for binomial distribution. In addition, the knowledge and practice of hookworm disease control were investigated among residents in Hejiang County and Wutongqiao District, Leshan City, Sichuan Province in 2021 and 2022, and the difference in the knowledge and practice of hookworm disease control was compared between members with and without familial aggregation of hookworm infections. Results A total of 66 812 residents from 25 196 households were sampled from main endemic areas of hookworm diseases in Sichuan Province from 2017 to 2022 for detection of hookworm infections, and 4 403 infections were identified (6.59% prevalence). The distribution of human hookworm infections in Sichuan Province did not fit the binomial distribution, and showed family aggregations (χ² = 2 116.759, P < 0.001). Family aggregation of human hookworm infections was found in endemic areas with 1% and higher prevalence of human hookworm infections (χ² = 136.006 to 428.738, all P values < 0.001), and family aggregation of human hookworm infections was identified in different years (χ² = 87.615 to 471.838, all P values < 0.001) and in different terrains of endemic areas (χ² = 8.423 to 1 144.176, all P values < 0.001). The members with hookworm infections had median eggs per gram of 180 (interquartile range, 780) in aggregated families and 72 (102) in non-aggregated families (Z = −2.686, P < 0.05). The proportion of members in families with aggregation of hookworm infections who knew the preventive measures of hookworm disease was significantly lower than in non-aggregated families (24.49% vs. 51.72%; χ² = 10.262, P < 0.05), and the proportion of members in families with aggregation of hookworm infections who often worked barefoot on the ground was significantly higher than in non-aggregated families (30.61% vs. 13.25%; χ² = 6.289, P < 0.05). Conclusions There is a familial aggregation of human hookworm infections in Sichuan Province, and awareness of preventive measures for hookworm disease and frequent working barefoot on the ground are associated with familial aggregation of hookworm infections.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To observe the effect of Renshen(ginseng)-Yuzhu(fragrant solomonseal rhizome)on inflammatory factors and inflammasomes in depression rats,and to explore the antidepressant mechanism of Renshen-Yuzhu.Methods Fifty male SD rats were divided into the blank group,model group,fluoxetine group(2.1 mg/kg),Renshen-Yuzhu low-dose group(1.89 g/kg),and Renshen-Yuzhu high-dose group(5.67 g/kg),with ten rats in each group.Except for the blank group,the rats in the other groups were treated with chronic unpredictable mild stress to establish a depression rat model.On the second day after the end of modeling,the rats in each group were given the corresponding drugs once daily for 14 days.After modeling and dosing,body weight,forced swimming immobility time,and sucrose preference rate were measured.After dosing,hematoxylin-eosin staining was used to detect neuronal damage in the cerebral cortex,enzyme-linked immunosorbent assay was used to detect the contents of interleukin-4(IL-4),interleukin-23(IL-23),and interleukin-27(IL-27)in cortex,real-time PCR was used to detect the mRNA expression of interleukin-24(IL-24)in cortex,and the protein expressions of nucleotide-binding oligomerization domain-like receptor protein 1(NLRP1),absent in melanoma 2(AIM2),and nucleotide-binding oligomerization domain-like receptor protein 4(NLRC4)were detected by Western blotting.Results After dosing,compared with the blank group,the body weight of the model group decreased,the sucrose preference rate decreased,the swimming immobility time was prolonged,the neuronal tissue in cortex was destroyed,the content of IL-4 in cortex decreased,the contents of IL-23 and IL-27 in cortex increased,and the protein expressions of NLRP1,AIM2 and NLRC4 in cortex increased(P＜0.01).Compared with the model group,the body weight of rats in each administration group increased,the sucrose preference rate increased,the swimming immobility time was shortened,the damage of neuronal tissues in cortex improved,the content of IL-4 in cortex increased,the contents of IL-23 and IL-27 in cortex decreased,and the protein expressions of NLRP 1,AIM2 and NLRC4 in cortex decreased(P＜0.05).Conclusion Renshen-Yuzhu couplet medicines can improve the depressive-like behavior and exert antidepressant effect in chronic stress rats,and its mechanism may be related to the inhibition of NLRP 1,NLRC4,AIM2 inflammasome activation and its mediated inflammatory response in cortex,reducing pro-inflammatory cytokines,and increasing the level of antiinflammatory cytokines.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

Sepsis-induced myocardial depression(SIMD),a common complication of sepsis,is one of the main causes of death in patients with sepsis.The pathogenesis of SIMD is complicated,and the process of SIMD remains incompletely understood,with no single or definitive mechanism fully elucidated.Notably,pyroptosis,as a pro-inflammatory programmed cell death,is characterized by Gasdermin-mediated formation of pores on the cell membrane,cell swelling,and cell rupture accompanied by the release of large amounts of inflammatory factors and other cellular contents.Mechanistically,pyroptosis is mainly divided into the canonical pathway mediated by caspase-1 and the non-canonical pathway mediated by caspase-4/5/11.Pyroptosis has been confirmed to participate in various inflammation-associated diseases.In recent years,more and more studies have shown that pyroptosis is also involved in the occurrence and development of SIMD.This article reviews the molecular mechanisms of pyroptosis and its research progress in SIMD,aiming to provide novel strategies and targets for the treatment of SIMD.

Objective To explore the establishment of a risk prediction model for concurrent bronchiolitis obliterans(BO)in children with refractory Mycoplasma pneumoniae pneumonia(RMPP).Methods A retrospective study included 116 RMPP children treated in the Department of Pediatrics of Xiangya Changde Hospital from June 2021 to December 2023.Eighty-one cases were allocated to the training set and thirty-five cases to the validation set based on a 7:3 ratio.Among them,26 cases in the training set developed BO,while 55 did not.The multivariate logistic regression was used to select variable factors for constructing the BO risk prediction model.Nomograms were drawn,and the receiver operating characteristic(ROC)curve was used to assess the discriminative ability of the model,while calibration curves and Hosmer-Lemeshow tests evaluated the model's calibration.Results Multivariate logistic regression analysis indicated that several factors were significantly associated with concurrent BO in RMPP children,including length of hospital stay,duration of fever,atelectasis,neutrophil percentage(NEUT%),peak lactate dehydrogenase(LDH),ferritin,peak C reactive protein(CRP),oxygenation index(PaO2/FiO2),≥2/3 lung lobe consolidation,pleural effusion,bronchial mucous plugs,bronchial mucosal necrosis,and arterial oxygen partial pressure(PaO2)(P<0.05).ROC curve analysis for the training set indicated an area under the curve of 0.904 with 88%sensitivity and 83%specificity;the validation set showed an area under the curve of 0.823 with 76%sensitivity and 93%specificity.The Hosmer-Lemeshow test's Chi-square values for the training and validation sets were 2.17 and 1.92,respectively,with P values of 0.221 and 0.196,respectively.Conclusions The risk prediction model for BO in RMPP children based on logistic regression has good performance.Variables such as length of hospital stay,duration of fever,atelectasis,peak LDH,peak CRP,NEUT%,ferritin,≥2/3 lung lobe consolidation,pleural effusion,bronchial mucous plugs,bronchial mucosal necrosis,PaO2/FiO2,and PaO2 can be used as predictors.

Spinal cord injury (SCI) is a devastating traumatic disease seriously impairing the quality of life in patients. Expectations to allow the hopeless central nervous system to repair itself after injury are unfeasible. Developing new approaches to regenerate the central nervous system is still the priority. Exosomes derived from mesenchymal stem cells (MSC-Exo) have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI, which are the key processes to rescue damaged spinal cord neurons and restore their functions. Nonetheless, MSC-Exo in SCI received scant attention. In this review, we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying mechanisms. Furthermore, we also focus on the application of exosomes as drug carrier in SCI. In particular, it combs the advantages of exosomes as a drug carrier for SCI, imaging advantages, drug types, loading methods, etc., which provides the latest progress for exosomes in the treatment of SCI, especially drug carrier.

A 41-year-old male was presented with rapidly progression memory impairment for 2 months and episodic limb shaking for 2 weeks as the main manifestations.Physical examination showed verbal disadvantage with decreased memory,attention,comprehension,and orientation.Serum vitamin B12 levels decreased,serum anti gastric parietal cell antibodies and anti-intrinsic factor antibodies were positive.Blood analysis showed macrocytic anemia,neuropsychological scale showed functional impairment in multiple cognitive domains,electrophysiological examination showed peripheral nerve damage,cerebrospinal fluid and imaging examination showed no abnormalities.The patient was diagnosed as having vitamin B12 deficiency dementia,vitamin B12 deficiency related involuntary movement and pernicious anemia.Supplementing with B vitamins and folic acid significantly improved cognitive impairment and eliminated symptoms of limb shaking.The purpose of this case report is to enhance the understanding of clinical doctors about dementia and involunting movement caused by vitamin B12 deficiency,in order to diagnose and treat it early.

Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1％after 1 course and 73.7％after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.