ObjectiveTo investigate the effect and mechanism of Yijingtang （YJT） in treating diminished ovarian reserve （DOR） in rats by regulating the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. MethodsFifty female SD rats with normal estrous cycles were randomly allocated into blank， model， low- and high-dose （12.579 and 25.158 g·kg^-1， respectively） YJT， and dehydroepiandrosterone （7.487 5 mg·kg^-1） groups， with 10 rats in each group. The rats in other groups except the blank group were administrated with the tripterygium glycosides tablet suspension （5 mg·kg^-1） by gavage for 14 days for the modeling of DOR. The rats in the drug treatment groups were administrated with corresponding drugs by gavage from day 15 for 30 consecutive days， and those in the blank and model groups received equal volumes of distilled water. The vaginal exfoliated cell smears were observed to assess the changes in the estrous cycle. The wet weight of bilateral ovaries was weighed for calculation of the ovarian index. Hematoxylin-eosin staining was performed to observe the histopathological changes in the ovaries and the proportions of follicles at various levels were calculated. The serum levels of sex hormones ［follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and anti-Müllerian hormone （AMH）］ and inflammatory factors ［tumor necrosis factor-alpha （TNF-α）， interleukin-1beta （IL-1β）， and interleukin-10 （IL-10）］ were determined by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction（Real-time PCR） was conducted to determine the mRNA levels of TLR4， MyD88， NF-κB profilin α （IκBα）， NF-κB and inflammatory factors in the ovarian tissue. Western blot was employed to measure the protein levels of factors related to the TLR4/MyD88/NF-κB signaling pathway in the ovarian tissue. Immunofluorescence （IF） was used to detect the nuclear translocation of NF-κB p65 in the ovarian tissue. ResultsCompared with the blank group， the model group showed disturbed estrous cycles， increased inflammatory infiltration in the ovarian tissue， decreases in ovarian index and proportion of presinusoidal follicles， and an increase in the proportion of atretic follicles （P<0.05， P<0.01）. In addition， the model group showed elevated serum levels of FSH， LH， TNF-α， and IL-1β， up-regulated mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.01）， lowered serum levels of AMH， E₂， and IL-10， down-regulated mRNA level of IL-10 （P<0.01）， and massive nuclear translocation of NF-κB p65 in the ovarian tissue. Compared with the model group， dehydroepiandrosterone and low and high doses of YJT restored the disturbed estrous cycle， reduced inflammatory infiltration in the ovarian tissue， increased the ovarian index （P<0.01）， and changed the follicular composition ratio （P<0.01）. Furthermore， the drugs lowered the serum levels of FSH， LH， TNF-α， and IL-1β， down-regulated the mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and the protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.05， P<0.01）， raised the serum levels of AMH， E₂， and IL-10， up-regulated the mRNA level of IL-10 （P<0.05， P<0.01）， and reduced the nuclear translocation of NF-κB p65 in the ovarian tissue. ConclusionYJT may inhibit the release and expression of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway to attenuate the inflammatory responses in the ovarian tissue， thereby improving the ovarian function in DOR rats.

ObjectiveTo investigate the effect and mechanism of Yijingtang （YJT） in treating diminished ovarian reserve （DOR） in rats by regulating the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway. MethodsFifty female SD rats with normal estrous cycles were randomly allocated into blank， model， low- and high-dose （12.579 and 25.158 g·kg^-1， respectively） YJT， and dehydroepiandrosterone （7.487 5 mg·kg^-1） groups， with 10 rats in each group. The rats in other groups except the blank group were administrated with the tripterygium glycosides tablet suspension （5 mg·kg^-1） by gavage for 14 days for the modeling of DOR. The rats in the drug treatment groups were administrated with corresponding drugs by gavage from day 15 for 30 consecutive days， and those in the blank and model groups received equal volumes of distilled water. The vaginal exfoliated cell smears were observed to assess the changes in the estrous cycle. The wet weight of bilateral ovaries was weighed for calculation of the ovarian index. Hematoxylin-eosin staining was performed to observe the histopathological changes in the ovaries and the proportions of follicles at various levels were calculated. The serum levels of sex hormones ［follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and anti-Müllerian hormone （AMH）］ and inflammatory factors ［tumor necrosis factor-alpha （TNF-α）， interleukin-1beta （IL-1β）， and interleukin-10 （IL-10）］ were determined by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction（Real-time PCR） was conducted to determine the mRNA levels of TLR4， MyD88， NF-κB profilin α （IκBα）， NF-κB and inflammatory factors in the ovarian tissue. Western blot was employed to measure the protein levels of factors related to the TLR4/MyD88/NF-κB signaling pathway in the ovarian tissue. Immunofluorescence （IF） was used to detect the nuclear translocation of NF-κB p65 in the ovarian tissue. ResultsCompared with the blank group， the model group showed disturbed estrous cycles， increased inflammatory infiltration in the ovarian tissue， decreases in ovarian index and proportion of presinusoidal follicles， and an increase in the proportion of atretic follicles （P<0.05， P<0.01）. In addition， the model group showed elevated serum levels of FSH， LH， TNF-α， and IL-1β， up-regulated mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.01）， lowered serum levels of AMH， E₂， and IL-10， down-regulated mRNA level of IL-10 （P<0.01）， and massive nuclear translocation of NF-κB p65 in the ovarian tissue. Compared with the model group， dehydroepiandrosterone and low and high doses of YJT restored the disturbed estrous cycle， reduced inflammatory infiltration in the ovarian tissue， increased the ovarian index （P<0.01）， and changed the follicular composition ratio （P<0.01）. Furthermore， the drugs lowered the serum levels of FSH， LH， TNF-α， and IL-1β， down-regulated the mRNA levels of TLR4， MyD88， IκBα， NF-κB， TNF-α， and IL-1β and the protein levels of TLR4， MyD88， p-IκBα， and p-NF-κB p65 （P<0.05， P<0.01）， raised the serum levels of AMH， E₂， and IL-10， up-regulated the mRNA level of IL-10 （P<0.05， P<0.01）， and reduced the nuclear translocation of NF-κB p65 in the ovarian tissue. ConclusionYJT may inhibit the release and expression of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway to attenuate the inflammatory responses in the ovarian tissue， thereby improving the ovarian function in DOR rats.

Blood biochemical indicators are an important basis for the diagnosis and treatment by doctors. The performance of related instruments, the qualification of operators, the storage method and time of blood samples and other factors will affect the accuracy of test results. However, it is difficult to meet the clinical needs of rapid detection and early screening of diseases with currently available methods. Point-of-care testing (POCT) is a new diagnostic technology with the characteristics of instant, portability, accuracy and efficiency. Microfluidic chips can provide an ideal experimental reaction platform for POCT. This paper summarizes the existing detection methods for common biochemical indicators such as blood glucose, lactic acid, uric acid, dopamine and cholesterol, and focuses on the application status of POCT based on microfluidic technology in blood biochemistry. It also summarizes the advantages and challenges of existing methods and prospects for development. The purpose of this paper is to provide relevant basis for breaking through the technical barriers of microfluidic and POCT product development in China.
Humans ; Point-of-Care Testing ; Lactic Acid/blood* ; Microfluidic Analytical Techniques/methods* ; Blood Glucose/analysis* ; Point-of-Care Systems ; Blood Chemical Analysis/instrumentation* ; Uric Acid/blood* ; Cholesterol/blood* ; Dopamine/blood* ; Microfluidics/methods*

Increasing evidence has underscored the significance of post-stroke alterations along gut-brain axis, while its role in pathogenesis and treatment of ischemic stroke (IS) remains largely unexplored. This study aimed to elucidate the therapeutic effects and action targets of Panax notoginseng saponins (PNS) on IS and explore a novel pathogenesis and treatment strategy of IS via profiling the microbial community and metabolic characteristics along gut-brain axis. Our findings revealed for the first time that the therapeutic effect of PNS on IS was microbiota-dependent. Ischemia/reperfusion (I/R) modeling significantly down-regulated Lactobacilli in rats, and PNS markedly recovered Lactobacilli, particularly Lactobacillus reuteri (L.Reu). Metabolomics showed a significant reduction in serum histidine (HIS) in clinical obsolete IS patients and rehabilitation period I/R rats. Meanwhile, the L.Reu colonization in I/R rats exhibited significant neuroprotective activity and greatly increased HIS in serum, gut microbiota, and brain. Moreover, exogenous HIS demonstrated indirect neuroprotective effects through metabolizing to histamine. Notably, vagus nerve severance in I/R rats was performed to investigate HIS's neuroprotective mechanism. The results innovatively revealed that PNS could promote HIS synthesis in gut by enhancing L.Reu proportion, thereby increasing intracerebral HIS through peripheral pathway. Consequently, our data provided novel insights into HIS metabolism mediated by L.Reu in the pathogenesis and treatment of IS.

ObjectiveTo investigate the social support status and influencing factors of schizophrenics in remission in Northeast Sichuan， and to provide ideas for improving their social support. MethodsFrom May to September 2020， a total of 533 patients who met the diagnosis criteria of the International Classification of Diseases， tenth edition （ICD-10） for schizophrenics in remission at the mental health institutions in Guangyuan， Bazhong and Dazhou cities were selected for the survey， and patients were assessed by self-made demographic and clinical data inventory and Social Support Rating Scale （SSRS）. Then the social support status of schizophrenic in remission and influencing factors were analyzed， meantime， the impact of the second round reimbursement policy of medical insurance benefits on their social support was addressed particularly. Results①The SSRS total score， objective support， subjective support， and utilization of support scores of schizophrenics in remission were lower than those of the national norm （t=5.065~30.382， P<0.01）. ②Univariate analysis showed that SSRS score was relatively high among patients with female gender （t=-3.632）， retired status （F=5.951）， married status （F=5.951）， spouse as primary caregiver （F=23.841）， annual household income >5 000 yuan （F=15.892）， patient's economic income （t=4.083）， and outpatient or online follow-up （F=3.954）， with statistically significant differences （P<0.05 or 0.01）. ③The total and dimensional scores of SSRS in patients with access to the second round medical insurance reimbursement were significantly higher than those without （t=10.195~25.103， P<0.01）. ④Multiple linear regression analysis denoted that gender， work status， marital status， primary caregivers， annual family income， economic income， follow-up visits and the second round medical insurance reimbursement were the factors influencing social support status of schizophrenics in remission （β=0.201~2.115， P<0.05 or 0.01）. ConclusionThe social support of schizophrenics in remission in Northeast Sichuan is below the national average， furthermore， their social support levels are affected by the gender， work status， marital status， primary caregivers， annual family income， economic income， follow-up visits and the second round medical insurance reimbursement， and the second round medical insurance reimbursement may ameliorate the social support status of patients.

【Objective】 To investigate the effect of two different blood transfusion strategies in non-shock stage of sever burn patients, so as to provide reference for clinical rational use of blood. 【Methods】 74 cases of severe burn patients in our hospital from July 2019 to December 2020 were randomly divided into restrictive transfusion group and liberal transfusion group. The differences of blood transfusion volume, red blood cell (RBC) count before and after blood transfusion, Hb value, incidence of transfusion adverse reactions, postoperative infection rate, length of hospital stay, and 30 day mortality between the two groups were retrospectively analyzed. 【Results】 1) The blood transfusion volume of the restricted blood transfusion group [(9.58±7.43)U] was statistically less than that of the liberal blood transfusion group [(22.24±20.08)U] (P<0.05). 2) The increase of Hb per unit of RBC in the restrictive transfusion group [(4.98±3.37)g/L] was higher than that in the liberal transfusion group [(3.28±3.12)g/L], and the difference was statistically significant. (P< 0.05). 3) There were no significant differences in postoperative infection rate, incidence of transfusion adverse reaction, length of stay and 30 day mortality between the two groups (P> 0.05). 【Conclusion】 Limited blood transfusion treatment for severe burn patients in non-shock stage can reduce the frequency and risk of blood transfusion and save blood resources, which is of great significance for rational and safe blood use in clinic.

Objective: Analysis of the effect of triggering receptor-1 expressed on myeloid cells (TREM-1) in nonalcoholic fatty liver disease (NAFLD) and the mechanism. Methods: The oleic acid-treated HepG2 cells were divided into model group, overexpression group, interference group A, interference group B and negative control group. The mouse model of NAFLD was generated and randomly divided into (nuclear factor-κB) NF-κB inhibition group, protein kinase B (AKT) inhibition group, knockout group A, knockout group B and control group. The expression of inflammatory factors and TREM-1 in liver tissue was detected by PCR, and fat accumulation was detected by oil red O staining. Western blotting was used to detect the expression of TREM-1 and signaling pathway proteins, and HE staining was used to detect liver tissue changes. Results: TREM-1 was up-regulated in liver tissue of NAFLD mice [(0.936±0.127) vs. (0.432±0.105)] and in oleic acid-treated HepG2 cells. In oleic acid-treated HepG2 cells, overexpression of TREM-1 increased inflammatory factor expression and increased lipid droplets; inhibition of TREM-1 expression decreased inflammatory factor expression, and lipid droplets decreased. Knockout of TREM-1 and inhibition of NF-κB in NAFLD mice reduced hepatocyte inflammatory factor expression and reduced liver damage; knockout of TREM-1 and inhibition of AKT reduced liver tissue lipids and drops accumulate. Conclusions The overexpression of TREM-1 in NAFLD mice liver tissue can regulate inflammatory factor expression and lipid droplets through NF-κB and AKT signal pathway. TREM-1 might be a potential therapeutic target of NAFLD.

Objective To investigate the changes of cortical thickness and relative resting state functional connectivity in patients with generalized anxiety disorder (GAD).Methods The present study analyzed structural and eyes-open resting state functional MRI were performed in 21 patients with GAD and 22 matched healthy controls.Cortical thickness was estimated with FreeSurfer.The structurally altered regions were defined as region of interest (ROI) to analyze functional connectivity (FC) using resting state functional MRI data by DPABI.Results Cortical thickness of patients with GAD were increased in right rostral middle frontal gyrus (rMFG;MNI:x =27.9,y =53.4,z =-11.1;size:241.93 mm2;FDR corrected,P ＜ 0.1) and right inferior temporal gyrus (IGT;MNI:x =49.7,y =-57.8,z =-8.7;size:138.93 mm2;FDR corrected,P＜0.1) compared with healthy controls.FC between right rMFG and right superior/middle occipital gyrus as well as well as FC between rMFG and right precentral gyrus showed decreased in patients with GAD compared with healthy controls(AlphaSim corrected,P＜0.05).FC between right rMFG and right angular gyrus showed increased in patients with GAD compared with healthy control (AlphaSim corrected,P＜0.05).Conclusion The rMFG may play an important role in the pathophysiology of GAD,which can be used as an stimuli target in physicotherapeutics to improve anxiety symptoms.

Objective To investigate the pathogenic and clinical features of bloodstream infections in patients with hematological malignancies for improving clinical treatment.Methods A total of 92 patients with hematological malignancy and positive blood culture treated during the period from September 2011 to September 2016 were analyzed,including clinical manifestations,treatment and prognosis.The distribution and antibiotic resistance of pathogens were also investigated.Results Of the 92 patients with bloodstream infection,64.1％ had underlying agranulocytosis.All patients had fever.Septic shock was found in 45.7％ cases.Elevated procalcitonin was detected in 82.6％ cases.The 107 isolates from blood stream included 75 (70.1％) strains of gram negative bacteria,27 (25.2％) strains of gram positive bacteria,and 5 (4.7％) strains of fungi.Escherichia coli showed higher resistance rate to ceftriaxone (80.9％) and levofloxacin (91.3％).Klebsiella pneumoniae (31.2％) and Acinetobacter baumannii (50.0％) strains showed relatively high resistance to imipenem.Gram positive bacteria were still sensitive to vancomycin and linezolid.Overall,35 (38.0％) patients died.The initial empirical treatment regimen had significant impact on patient outcome (P＜0.05).The mortality rate of initial carbapenem-based empirical treatment was slightly lower (28.6％ vs 46.2％) than that of non-carbapenem-based initial regimen,but the difference was not significant (P=0.163).Conclusions The outcome is poor in patients with hematological malignancy complicated with bloodstream infection.The main pathogen is gram negative bacteria in such infections,associated with high antibiotic resistance.The emergence of carbapenem resistance is an issue of concern.The effectiveness of initial empirical therapy may have significant effect on patient outcome.

Objective To study the pharmacokinetic status of Cyclophosphamide (CYC) in children with lupus nephritis (LN),as well as the relationship between the pharmacokinetic results and clinical indicators,adverse reactions,curative effect evaluation.Methods Thirty patients hospitalized at Tianjin Children's Hospital from January 2014 to December 2016 were treated with glucocorticoid (GC) combined with CYC.Blood samples were collected in 6 point-in-time after intravenous CYC,a high performance liquid chromatography (HPLC) method was used to detect the blood drug concentration,and the pharmacokinetic results were calculated.All patients were followed up for 24 weeks,and the levels of serum albumin (ALB),24 hours urinary protein,serum creatinine (Scr),complement 3 (C3),therapeutic effect and systemic lupus erythematosus disease activity index scores were evaluated at the same time.Results Pharmacokinetic curve showed the second chamber model,the area under the curve (AUC) of time-effect relationship was (143.55 ±42.43) g/(L · h),peak concentration (Cmax) was (20.02 ± 3.55) g/L,and half-time period (T1/2) was(4.21 ± 0.96) h.Age and gender had no influence on AUC,Cmax and T1/2,and statistically significant correlation was found between serum ALB and T1/2,which was positively correlated (r =0.517,P ＜ 0.05).After 16 weeks of treatment,7 patients were partially responsive,22 cases had a complete remission,and the invalid case was only one.Followed up for 24 weeks,6 patients were partially responsive,24 cases had a complete remission.After 16 weeks of treatment,there were statistical differences in AUC among patients with complete response,partial response or no remission.And after 24 weeks,the patients between complete remission and partial remission had no statistically significant difference in the AUC.After 16 weeks and 24 weeks,T1/2 and Cmax had no statistical differences among those groups of patients.Adverse reactions included leukopenia (3 cases,10.00％),gastrointestinal symptoms (4 cases,13.33％) and respiratory tract infection (6 cases,20.00％).There was no statistical relationship between pharmacokinetic parameters and the occurrence of adverse reactions.Single factor analysis showed that there was a statistical significance between ALB,urine protein quantity and treatment effect,but multi-factor analysis showed that the relation between factors and therapeutic effect had no statistical significance.Conclusions HPLC method can be used for the detection of cyclophosphamide blood drug concentration.The cyclophosphamide pharmacokinetic status of children and adult is similar.ALB and T1/2 show a linear positive correlation.Single factor analysis shows a correlation between ALB and treatment effect.Therefore,the increasing level of plasma propagated before treatment can improve therapeutic effect possibly.Cyclophosphamide pharmacokinetic status has nothing to do with the occurrence of adverse drug reactions in the study.