Aim To screen and study the expression of long non-coding RNA (IncRNA) in rats with middle cerebral artery occlusion (MCAO) with MCAO treated with Tao Hong Si Wu decoction (THSWD) and determine the possible molecular mechanism of THSWD in treating MCAO rats. Methods Three cerebral hemisphere tissue were obtained from the control group, MCAO group and MCAO + THSWD group. RNA sequencing technology was used to identify IncRNA gene expression in the three groups. THSWD-regulated IncRNA genes were identified, and then a THSWD-regu-lated IncRNA-mRNA network was constructed. MCODE plug-in units were used to identify the modules of IncRNA-mRNA networks. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the enriched biological functions and signaling pathways. Cis- and trans-regulatory genes for THSWD-regulated IncRNAs were identified. Reverse transcription real-time quantitative pol-ymerase chain reaction (RT-qPCR) was used to verify IncRNAs. Molecular docking was used to identify IncRNA-mRNA network targets and pathway-associated proteins. Results In MCAO rats, THSWD regulated a total of 302 IncRNAs. Bioinformatics analysis suggested that some core IncRNAs might play an important role in the treatment of MCAO rats with THSWD, and we further found that THSWD might also treat MCAO rats through multiple pathways such as IncRNA-mRNA network and network-enriched complement and coagulation cascades. The results of molecular docking showed that the active compounds gallic acid and a-mygdalin of THSWD had a certain binding ability to protein targets. Conclusions THSWD can protect the brain injury of MCAO rats through IncRNA, which may provide new insights for the treatment of ischemic stroke with THSWD.

ObjectiveTo investigate the acute effects of compound air pollution on children’s respiratory function. MethodsUsing panel group study design， 223 students in five classes of grade 4 from two primary schools （a， b） in Xuhui and Hongkou districts of Shanghai were randomly selected to measure pulmonary function and exhaled nitric oxide （FeNO）. The first three tests were carried out from May to June in 2020， and the fourth test was carried out from September to December in 2021. At the same time， the daily and hourly mean values of PM_2.5， PM₁₀， SO₂， NO₂， O₃ and CO was collected from the nearby air quality monitoring points of the two schools during the same period ， as well as meteorological monitoring data （temperature， humidity， wind speed and atmospheric pressure）. The linear mixed effect model was used to analyze the effects of air pollution on pulmonary function and respiratory inflammation in the summer. ResultsThe results of single pollutant model showed that PM_2.5， PM_10， SO₂ and NO₂ were positively correlated with FeNO， and the effect was reflected in lag0， lag1 and lag3 （P<0.05）. PM_2.5， PM₁₀ and NO₂ were negatively correlated with the changes of lung function FEF_25%， FEF_50%， FEF_75%， FeF_25%-75%， PEF， FVC， FEV1 and FEV1/FVC， and the effect was reflected in lag0 to lag3 days （P<0.05）. The results of the dual pollutant model showed that the concentration changes of SO₂ and NO₂ were significantly correlated with the decrease of FEV1 when combined with O₃ or PM_2.5 （P<0.01）， and the concentration changes of PM_2.5 was significantly correlated with the increase of FeNO when O₃， SO₂ and NO₂ were combined respectively （P<0.01）. The effects of the dual pollutant model were greater than the effect of PM_2.5 single pollutant model. ConclusionThe health effects of different air pollutants on children’s respiratory tract function indexes in summer are different. The combined effects of two pollutants on the lung function of children increased to different degrees. Although air pollution is light in summer， it still has an impact on children’s respiratory tract function index and inflammation index， and the combined effect of dual pollutants is more significant than that of single pollutant.

OBJECTIVE To study the effects of methimazole on the urinary metabolomics of hyperthyroidism rats， and to preliminarily investigate its possible mechanism. METHODS Thirty SD rats were randomly divided into control group， model group and methimazole group， with 10 rats in each group. Except for the control group， the rats in the other two groups were given Levothyroxine sodium tablets 160 mg/kg by intragastric administration for 15 days； at the same time， methimazole group was additionally given methimazole 3.6 mg/kg daily by intragastric administration every day. The basic condition of the rats was observed， and the body weight and anal temperature were measured. After the last medication， the serum levels of triiodothyronine （T3）， tetraiodothyronine （T4）， free triiodothyronine （FT3）， free tetraiodothyronine （FT4）， and thyroid stimulating hormone （TSH） were determined； 24-hour urine was collected on the 15th day after administration. UPLC-TOF-MS was used to analyze the urine metabolomics of rats. Principal component analysis and orthogonal partial least squares-discriminant analysis were used to screen out related differential metabolites， and potential metabolic pathways were analyzed by using HMDB and KEGG. RESULTS Compared with the control group， the rectal temperature， serum levels of T3， T4， FT3 and FT4， the expressions of differential metabolites sebacic acid， cholic acid 3-O-glucuronic acid and N6， N6， N6-trimethyl-L-lysine in urine were significantly up-regulated， while body weight， serum level of TSH， the expressions of deoxycytidine and 2-oxo-4-methylthiobutanoic acid in urine were significantly down-regulated （P＜0.01）. Compared with model group， above indexes of rats were reversed significantly in methimazole group （P＜0.01 or P＜0.05）. Above five differential metabolites were mainly involved in four signaling pathways: pentose and glucuronate interaction， lysine degradation， cysteine and methionine metabolism， and pyrimidine metabolism. CONCLUSIONS Methimazole might improve hyperthyroidism by modulating the four pathways of pentose and glucuronate interaction， lysine degradation， cysteine and methionine metabolism， and pyrimidine metabolism.

Objective To analyze the clinical efficacy of the Qianyang Fengsui Dan(combined with flying needle therapy)in the treatment of kidney-yang deficiency type of insomnia.Methods A retrospective study was conducted to select 82 patients with insomnia admitted to the Department of Traditional Chinese Medicine of Dezhou Hospital of Traditional Chinese Medicine from November 2020 to November 2021,and they were divided into an observation group and a control group according to whether or not they were treated with Qianyang Fengsui Dan combined with flying needle therapy,with 41 cases in each group.The control group was treated with Estazolam,while the observation group was treated with Qianyang Fengsui Dan combined with flying needle therapy on the basis of the treatment of the control group,and the course of treatment was 1 month.The changes of Pittsburgh Sleep Quality Index(PSQI)scores and Epworth Sleepiness Scale(ESS)scores,as well as polysomnographic parameters were observed before and after treatment in the two groups.The changes of γ-aminobutyric acid(GABA),glutamate(GA),substance P(SP),and neuropeptide Y(NPY)levels were compared before and after treatment between the two groups.And followed up for 1 year to compare the incidence of relapce of the two groups of patients.Results(1)The total effective rate was 95.12%(39/41)in the observation group and 63.41%(26/41)in the control group,and the efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,PSQI scores and ESS scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving PSQI scores and ESS scores,and the differences were statistically significant(P＜0.05).(3)After treatment,sleep efficiency,awakening time,sleep latency,REM,and total sleep time were significantly improved in the two groups(P＜0.05),and the observation group was significantly superior to the control group in improving sleep efficiency,awakening time,sleep latency,REM,and total sleep time,and the differences were statistically significant(P＜0.05).(4)After treatment,the serum GABA,GA,SP,and NPY levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the serum GABA,GA,SP,and NPY levels,and the differences were all statistically significant(P＜0.05).(5)After treatment,follow-up for 1 year,the recurrence rate of the observation group was 0,and there were 7 cases of recurrence in the control group,and the recurrence rate of the control group was 17.07%(7/41),and the recurrence rate of the observation group was lower than that of the control group,and the difference was statistically significant(P＜0.05).Conclusion The combination of flying needle therapy and Qianyang Fengsui Dan can effectively relieve insomnia and fatigue in patients with insomnia,reduce daytime drowsiness,regulate the release of blood monoamine neurotransmitters,and reduce the relapse rate,and its efficacy is superior to that of simple western medicine treatment.

OBJECTIVE To observe the short-term efficacy and safety of venetoclax combined with homoharringtonine and cytarabine in the treatment of acute myeloid leukemia （AML）. METHODS The data of 40 newly diagnosed AML patients admitted to our hospital from October 2022 to November 2023 were retrospectively collected and divided into observation group and control group according to treatment plan， with 20 cases in each group. The patients in the control group were given Daunorubicin hydrochloride for injection+Cytarabine for injection， and the patients in the observation group were given Venetoclax tablets+ Homoharringtonine injection+Cytarabine for injection. The patients in both groups were given relevant medicine， with 28 days as one cycle. The short-term efficacy， negative rate of minimal residual disease （MRD）， duration of granulocyte deficiency， duration of platelet （PLT） ＜20×109 L－1， transfusion volume of suspended red blood cells and platelet， and the occurrence of adverse drug reactions were evaluated in both groups after 1 cycle of induction chemotherapy. RESULTS The complete remission or complete remission with incomplete hematologic recovery （CR/CRi） rate in the observation group was significantly higher than control group （P＜0.05）， and the negative rate of MRD in the observation group was also significantly higher than control group （P＜0.05）. However， in low-， medium- and high-risk patients， there was no statistical significance in CR/CRi rates between the two groups （P＞0.05）. There were no significant differences in the duration of agranulocytosis， the duration of PLT ＜20×109 L－1， the amount of suspended red blood cell transfusion， the amount of platelet transfusion， the incidence of hematologic toxicity and the incidence of non-hematologic toxicity between 2 groups （P＞0.05）. CONCLUSIONS Venetoclax combined with homoharringtonine and cytarabine show good short-term efficacy and safety in the treatment of AML.

【Objective】 To investigate additional exclusion criteria for therapeutic apheresis erythrocytes and the possibility of adverse reactions by analyzing the occurrence of rare adverse reactions in two patients who underwent therapeutic erythrocytes apheresis. 【Methods】 Erythrocytes were harvested by apheresis from two patients with indications for therapeutic erythrocytes collection for preservation or discarding. 【Results】 One case experienced persistent atrial fibrillation and a gout attack after the collection, while another case experienced persistent hypotension during the collection and a subsequent reduction in haemoglobin levels after collection 【Conclusion】 To reduce the incidence of adverse reactions, it is essential to have strict exclusion criteria for therapeutic erythrocytes apheresis and to enhance the monitoring of whole collection process in patients with atrial fibrillation and gout.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To investigate the protective effect of butyrolphthalein on nerve injury in rats with acute cerebral infarction(ACI)by regulating Toll-like receptor 4(TLR4)/nuclear transcription factor-κB(NF-κB)pathway.Methods SD rats were randomly divided into model group and experimental-L,-M,-H groups;ACI models were established in vivo except sham operation group.The experimental-L,-M,-H groups were given 20,40,80 mg·kg-1 butylphthalide,qd,for 7 days;the sham operation group and the model group were given the same amount of 0.9％NaCl,for 7 days.Neural function score,bilateral sticker removal time,balance beam crossing score,cerebral water content and cerebral infarction volume of rats in each group were measured.The expression of axonal growth inhibitory factor A(Nogo-A)and serum inflammatory factor in hippocampus were detected by enzyme-linked immunosorbent assay(ELISA).The expression of TLR4/NF-κB pathway related proteins was detected by Western blot.Results The neural function scores of sham operation group,model group,and experimental-L,-M,-H groups were 0,3.55±0.52,2.55±0.52,1.82±0.60,0.91±0.30,respectively;the Nogo-A in hippocampus were(0.93±0.23),(6.32±0.53),(5.10±0.55),(3.54±0.57),(1.58±0.30)ng·L-1,respectively;serum Nogo-A were(0.49±0.12),(5.09±0.82),(3.83±0.54),(2.23±0.64),(1.13±0.25)ng·L-1,respectively;TLR4 protein expression were 0.44±0.05,1.23±0.14,0.93±0.07,0.75±0.06,0.55±0.07,respectively;the expressions of p-p65 NF-κB protein were 0.32±0.05,0.82±0.06,0.68±0.08,0.57±0.07,0.44±0.05,respectively.There were statistically significant differences between sham operation group and model group(all P＜0.05).There were significant differences in the above indexes between the model group and the experimental-L,-M,-H groups(P＜0.05).Conclusion Butylphthalein can play a neuroprotective role in ACI rats by regulating TLR4/NF-κB pathway to improve nerve function and reduce inflammatory damage.

Objective To explore the protective mechanism of icariin on neuronal oxidative damage,providing a basic pharmacological basis for the treatment of cognitive impairment.Methods Glutamate was used to induce oxidative stress injury in HT22 cells.HT22 cells were divided into control group(normal cultured cells),model group(glutamate injury model)and experimental-L,-M,-H groups(5,10 and 20 μmol·L-1 icariin pretreatment for modeling,respectively).Cell proliferation was detected by cell counting kit-8(CCK-8)method;cytotoxicity was detected by lactate dehydrogenase(LDH)method;reactive oxygen species(ROS)levels were detected by flow cytometry;superoxide dismutase(SOD)levels were detected by biochemical kits;the expression levels of Kelch-like epichlorohydrin-related protein-1(Keap1),nuclear factor E2-related factor 2(Nrf2)were detected by Western blotting;the corresponding mRNA expression was detected by real-time fluorescence quantification polymerose chain reaction.Results The cell viability of control group,model group and experimental-L,-M,-H groups were(100.00±1.31)％,(66.38±2.44)％,(72.07±4.95)％,(82.41±3.57)％and(87.97±4.98)％;LDH release were(0.48±0.52)％,(18.82±2.09)％,(15.32±1.17)％,(10.37±1.39)％and(6.51±0.87)％;ROS level were(14.23±1.13)％,(41.74±1.60)％,(35.69±1.08)％,(33.28±1.69)％and(30.32±2.03)％;SOD levels were(54.84±1.17),(37.95±1.13),(48.02±1.28),(50.56±1.34)and(52.55±1.04)U·mg-1;Keap1 protein levels were 0.36±0.01,0.52±0.03,0.46±0.04,0.39±0.09 and 0.35±0.12;Nrf2 protein levels were 0.29±0.02,0.13±0.08,0.18±0.03,0.21±0.11 and 0.26±0.04;catalase(CAT)mRNA levels were 1.01±0.08,0.81±0.06,0.90±0.04,1.05±0.15 and 1.33±0.26;SOD mRNA levels were 1.09±0.12,0.83±0.03,0.86±0.08,0.94±0.08 and 1.09±0.16.Among the above indicators,the differences between the model group and the control group were statistically significant(all P＜0.01);the differences between the experimental-M,-H groups and the model group were statistically significant(P＜0.01,P＜0.05).Conclusion Icariin may activate the Keap1/Nrf2/antioxidant response element(ARE)signaling pathway,regulate the expression of related proteins,and reduce the level of ROS to effectively alleviate oxidative stress injury in neuronal cells.

Objective To explore the anti-inflammatory mechanism of the active ingredients of Gubi Formula in treating osteoarthritis.Methods Normal human chondrocytes were cultured in vitro,and lipopolysaccharide(LPS)stimulated inflammation.The cells were divided into control group(normal culture),model group(10 μg·mL-1 LPS),quercetin group(10 μg·mL-1 LPS+8 μmol·L-1 quercetin),formononetin group(10 μg·mL-1 LPS+50 μmol·L-1 formononetin),naringin group(10 μg·mL-1 LPS+10 μmol·L-1 naringin),asperosaponin Ⅵ group(10 μg·mL-1 LPS+50 pmol·L-1 asperosaponin Ⅵ),β-ecdysterone group(10 μg·mL-1 LPS+50 μmol·L-1β-ecdysterone).Cell counting kit-8(CCK8)was used to detect the viability of chondrocytes.Western blot was used to detect the expression of nuclear factor NF-kappa-B p65 subunit(p65),nuclear factor erythroid 2-related factor 2(Nrf2)nuclear protein.Results The cell viability of control group,model group,quercetin group,formononetin group,naringin group,Dipsacoside Ⅵ group,β-ecdysterone group were(103.10±8.55)％,(62.41±2.35)％,(76.92±1.74)％,(77.01±0.60)％,(80.39±3.06)％,(79.43±0.94)％,(55.20±0.99)％;the relative expression of Nrf2 protein were 1.00±0.00,1.01±0.09,1.30±0.15,0.91±0.15,1.23±0.25,0.71±0.19,1.51±0.13,1.26±0.15;the relative expression of P65 protein were 1.00±0.00,2.24±0.85,0.74±0.33,1.49±0.29,0.97±0.06,1.33±0.07,1.67±0.22,1.52±0.17;the relative expression of inflammatory mediators iNOS were 1.00±0.00,1.52±0.27,1.07±0.24,1.25±0.12,1.01±0.30,1.44±0.12,1.07±0.18,1.11±0.16.The above indexes in quercetin group,formononetin group and naringin group were significantly different from those in model group(P＜0.05,P＜0.01 and P＜0.001).Compared with the model group,there was no significant difference in the above indexes between the Asperosaponin Ⅵ group and theβ-ecdysterone group(all P＞0.05).Conclusion The active components of Gubi Formula,including quercetin,mangiferin,and naringin,can activate Nrf2-HO-1 signaling and inhibit the activation of the Nuclear factor-κB(NF-κB)pathway plays an anti-inflammatory role in alleviating osteoarthritis.