Aim To study the neuroprotective effects of Herba siegesbeckiae extract on cerebral ischemia/ reperfusion rats and its mechanism. Methods Sixty SD rats were randomly divided into model group, low, middle and high dose groups of Herba siegesbeckiae, and Sham operation group, and the drug was given continuously for seven days. The degree of neurologic impairment was evaluated by mNSS, and the infarct volume was measured by MRI. The number of Nissl-posi- tive cells was detected by Nissl staining, and the apop- tosis was accessed by Tunel staining. Furthermore, the expression of Bax, Bcl-2 and NeuN was observed by Western blot, and the expression of NeuN was detected by immunofluorescence staining. The expression of IL- 1β, TNF-α and IL-6 mRNA was performed by RT- qPCR. Results The mNSS score and the volume of ischemic cerebral infarction in the model group were significantly increased, and Herba siegesbeckiae extract treatment significantly decreased the mNSS score and infarct volume (P<0.05, P<0.01). Herba siegesbeckiae extract could increase the number of Nissl-pos- itive cells and the expression of NeuN (P<0.01), and reduce the number of Tunel-positive cells (P<0.01). Western blot showed that Herba siegesbeckiae extract inhibited the expression of Bax, increased Bcl-2 and NeuN in ischemic brain tissue (P<0.01). RT-qPCR showed that Herba siegesbeckiae extract inhibited the expression of IL-1 β, TNF-α and IL-6 mRNA in the is-chemic brain tissue (P<0.01). Conclusions Herba siegesbeckiae extract can reduce the cerebral infarction volume, improve the neurological function damage, inhibit the apoptosis of nerve cells and the expression of inflammatory factors and promote the expression of NeuN, there by exerting protective effects on MCAO rats.

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndrome elements in the patients with diarrhea-predominant irritable bowel syndrome(IBS-D)overlapping functional dyspepsia(FD),and to explore the characteristics of TCM syndromes in IBS-D overlapping FD.Methods Clinical investigation was performed for collecting the clinical data of patients with IBS-D,FD and IBS-D overlapping FD(overlapping group),50 cases for each disease.The TCM syndrome elements were analyzed by syndrome-element dialectical methods,and the characteristics of TCM syndromes and syndrome types were summarized by frequency analysis,association rule analysis and cluster analysis.Results(1)The results of frequency analysis showed that emotional disorder was the main inducing or aggravating factor in the overlapping group,followed by improper diet.The primary syndromes in the overlapping group were diarrhea,abdominal distension,epigastric fullness,abdominal pain and postprandial fullness;the tongue color was usually pale,pale red,dark or red,the tongue body was usually enlarged or tooth-marked,and the tongue coating was usually thin white or white;slippery pulse,wiry pulse,deep pulse and thin pulse were the common pulses.The diseases-location syndrome elements mainly involved spleen,stomach,small intestine and liver,and the disease-nature syndrome elements mainly involved qi stagnation,dampness,qi deficiency and yang deficiency.(2)The results of association rule analysis showed that the combination of abdominal distension and diarrhea had the highest support(accounting for 70.00％)associated with TCM syndromes,the combination of spleen and stomach had the highest support(accounting for 80.00％)associated with diseases-location syndrome elements,the two combinations of dampness and qi stagnation,qi deficiency and qi stagnation had the highest support(both accounting for 36.00％)associated with disease-nature syndrome elements.(3)The results of cluster analysis showed that TCM syndromes in the overlapping group were clustered into four categories of syndrome manifestations,namely spleen deficiency and dampness stagnation syndrome,spleen deficiency and qi stagnation syndrome,spleen yang deficiency syndrome and spleen qi deficiency syndrome;the combinations of syndromes and syndrome elements were clustered into five categories,namely manifestations of liver depression and spleen deficiency syndrome combined with intestinal dampness stagnation syndrome,manifestations of food stagnation in the stomach syndrome,manifestations of spleen deficiency and qi stagnation syndrome,manifestation of greasy coating,and manifestations of stomach qi failing to descend and rebellious stomach qi syndrome.Conclusion IBS-D overlapping FD usually affects the spleen,and is closely related to the disorders of the stomach,liver and small intestine.The main syndromes of IBS-D overlapping FD are spleen deficiency and dampness stagnation syndrome,and liver stagnation and spleen deficiency combined with intestinal dampness stagnation syndrome.Qi stagnation and dampness stagnation contribute to the key pathogenesis of IBS-D overlapping FD.IBS-D overlapping FD is characterized by the mixture of deficiency and excess,with the presence of pathological products such as phlegm-dampness,food accumulation and blood stasis in the later stage.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Objective To construct time-series by adopting autoregressive integrated moving average(ARIMA)model for analyzing the trend and genotype characteristics of single-center human papillomavirus(HPV)infection in Tianjin area.Methods A total of 7 236 female patients who underwent HPV testing in a hospital from January 2018 to December 2022 were selected.HPV infection status and genotype distribution in Tianjin area from 2018 to 2022 were compared.ARIMA model time-series was constructed,and model fitting was analyzed.The number of HPV infections in 2023 was predicted and compared with the actual occurrence,the predictive performance of the model was evaluated.Results HPV infection rate in Tianjin area from 2018 to 2022 was 14.41％,with the highest rate(15.47％)in the age group of 31-40 years.Among the positive specimens,the proportion of single type HPV infection was the highest,accounting for 73.54％(767/1 043),with high-risk HPV being the main type.The highest infection rates of low-risk and high-risk types were type HPV-6(2.59％)and type HPV-16(16.06％),re-spectively.ARIMA model was constructed,and the optimal model was ARIMA(0,1,2)(0,1,1)12,with akaike in-formation criterion(AIC)and bayesian information criterion(BIC)values of 3.877 and 4.005,respectively.There was no statistical significance in Ljung-Box Q=8.828 showed by white noise test(P＞0.05).The number of HPV infection in 2023 was predicted by the model.The overall trend of the actual value and the predicted value was basi-cally consistent,RMSE,MAPE and MAE of the model were 6.289,34.149 and 4.706,respectively,suggesting that the model had a good prediction effect.Conclusion Among the female population in Tianjin area,HPV infec-tion is mainly caused by single,high-risk type,with HPV-16 having the highest infection rate.There is seasonal variation in HPV infection in Tianjin.ARIMA model has good prediction effect on the prevalence trend of HPV in-fection,which is suitable for short-term prediction.

Aim To study the permeability of salidro-side(Sal)to the blood brain barrier(BBB)by high-performance liquid chromatography electrospray ioniza-tion tandem mass spectrometry(UPLC-ESI-MS-MS),and to explore the target and mechanism of Sal in the treatment of ischemic stroke(IS)by network pharma-cology,molecular docking technique and animal exper-iment.Methods UPLC-ESI-MS/MS was used to study the BBB penetration of Sal.Multiple databases were used to predict the target of Sal and the disease target of IS,GO and KEGG enrichment analysis were performed and verified by molecular docking technique and animal experiments.Results After Sal adminis-tration to normal rats and MCAO rats,Sal prototype and the metabolite tyrosol were detected in plasma and brain tissue of rats.A total of 191 targets were identi-fied by network pharmacology,the enrichment analysis of GO mainly involved in the biological processes of proteolysis and positive regulation of cell migration,and the analysis of KEGG pathway suggested that PI3K-Akt,MAPK,FOXO and other signaling path-ways played a key role in the treatment of IS by Sal The results of molecular docking showed that Sal had good binding ability with the core target of docking,and the results of animal experiments showed that Sal could significantly improve the neurologic impairment of MCAO rats,the number of Nissl-positive cells in is-chemic side significantly increased,and the expression of VEGF,EGFR and IGF1 increased,while the ex-pression of IL-6 and MMP9 was inhibited.Conclu-sions Sal is able to penetrate the BBB and enter the central nervous system for its pharmacological effects.Network pharmacology predicts the core targets of Sal in the treatment of IS,including VEGFA,EGFR,IL-6,MMP9,IGF1,CASP3,ALB,SRC.The effects of Sal on some core targets can be verified by animal ex-periments,to provide a reference for further study of the mechanism of Sal in the treatment of IS.

This study identified the anti-depression targets of Kaixin San(KXS) in the brain tissue with "target fishing" strategy, and explored the target-associated pharmacological signaling pathways to reveal the anti-depression molecular mechanism of KXS. The Balb/c mouse model of depression was established by chronic unpredictable mild stress(CUMS) and the anti-depression effect of KXS was evaluated by forced swimming test and sucrose preference test. KXS active components were bonded to the benzophenone-modified magnetic nanoparticles by photocrosslinking reaction for capturing target proteins from cortex, thalamus and hippocampus of depressive mice. The target proteins were identified by liquid chromatography-mass spectrometry/mass spectrometry(LC-MS/MS). The enrichment analysis on signaling pathways was performed by Cytoscape. The potential biological functions of targets were verified by immunohistochemistry and Western blot assay. The results showed that KXS significantly improved the behavioral indexes. There were 64, 91, and 44 potential targets of KXS identified in cortex, thalamus, and hippocampus, respectively, according to the target identification experiment. The functions of these targets were mainly associated with vasopressin-regulated water reabsorption, salmonella infection, thyroid hormone synthesis, and other signaling pathways. Besides, the results of immunohistochemistry and Western blot showed that KXS up-regulated the expressions of argipressine(AVP) in the cortex, heat shock protein 60(HSP60), cytochrome C oxidase 4(COX4), and thyrotropin-releasing hormone(TRH) in the thalamus, and down-regulated the expressions of tumor necrosis factor-α(TNF-α) and nuclear factor kappa B(NF-κB) p65 in the thalamus. Therefore, KXS may exert anti-depression effect through regulating vasopressin signaling pathway in the cortex and inflammation, energy metabolism, and thyroid hormone signaling pathways in the thalamus, and the effect of KXS on hippocampus is not significant.
Animals ; Mice ; Chromatography, Liquid ; Disease Models, Animal ; Drugs, Chinese Herbal/chemistry* ; Hippocampus ; Stress, Psychological/drug therapy* ; Tandem Mass Spectrometry ; Depression/drug therapy*

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Aim To study the effect of salidroside (SAL) on cerebral vascular endothelial cells of rats with ischemic brain injury and its mechanism of action. Methods Twenty-four healthy adult SD male rats were prepared by bolt plugging method to prepare MCAO models,and randomly divided into sham surgery group ( Sham ) , model group ( MCAO ) , and SAL administration group (MCAO + SAL) ,and the concentration of SAL was 50 mg • kg ~ , with a continuous administration for six days. Western blot was used to detect the protein expression of ICAM-1, VCAM-1 , E-se-lectin,and P-selectin in injured brain tissue of rats. In vitro cell experiments using HUVECs were subjected to different concentrations of salidroside (0. 1,1,10 jjunol • L ) and LPS (100 ^g • L ) intervened for 24 hours,and CCK-8 was employed to detect the effects of SAL and LPS on the survival of HUVECs. In vitro an-giogenesis experiments, LPS group ( 100 (jLg • L~ ) and SAL administration group ( LPS + Sal) intervened in HUVECs for 24 hours,and the concentrations of SAL administration were 0. 1,1, and 10 jjunol • L , then the effects of LPS and SAL on their angiogenesis were observed. The protein expressions of ICAM-1, VCAM-1 ,E-selectin,and P-selectin in HUVECs were detected by Western blot. Results SAL could reduce the expression of ICAM-1, VCAM-1, E-selectin, and P-selectin in ischemic brain tissue of MCAO rats. In vitro experimental studies found that salidroside had no effect on the survival of HUVECs. LPS inhibited the angiogenesis of HUVECs, and after the action of SAL, SAL (1,10 jjimol • L ) reversed the effect of LPS and promoted its angiogenesis. Compared with the control group,the expressions of ICAM-1, VCAM-1, E-selectin and P-selectin of HUVECs after LPS stimulation increased, while the expressions of ICAM-1, VCAM-1 , E-selectin and P-selectin were significantly reduced after the addition of SAL, which promoted the angiogenesis ability of HUVECs. Conclusions SAL can improve the ability of cell regeneration in rats with ischemic brain injury and promote the ability of blood vessel formation.

Aim To explore the effect of γ-ray on the mRNA,protein expression levels and metabolic activity level of the key drug metabolic enzyme CYP3A1 in rat liver. Methods Wistar rats were randomly divided into control group, 24 h post-radiation group and 72 h post-radiation group. The experimental group was exposed to total body irradiation of single 6 Gy γ-ray. Blood was collected from the orbital venous plexus for blood routine examination and biochemical analysis 24 h and 72 h after irradiation, and liver tissue was prepared for quantifying expression of CYP3A1 mRNA and liver-specific microRNA (miR-122-5p) through RT-PCR. The expression level of CYP3A1 protein was analyzed by Western blot, and the metabolic activity level of CYP3A1 detected by the specific substrate midazolam combined with LC-MS method. Results Com¬pared with the control group, the weights of the rats in the radiation group significantly decreased, and the number of white blood cells was markedly reduced. Simultaneously, the activities of alanine aminotrans-ferase and alkaline phosphatase continuously descended, as well as the levels of total bilirubin and bile acid significantly increased, which indicated that the liver may be damaged after radiation. The relative expression of CYP3A1 mRNA continued to increase significantly 24 h and 72 h after irradiation. CYP3A1 protein expression and metabolic activity levels showed an obvious increasing trend 24 h after irradiation, and rose significantly 72 h after irradiation compared with the control group. At the same time, the expression of miR-122-5p in liver of rats in the 24 h and 72 h post-radiation group continued to decrease rapidly compared with the control group. Conclusions γ-ray radiation may arouse damage effect on liver, which leads to the continuous up-regulation of the mRNA and protein expression levels of the capital metabolic enzyme CYP3A1 in liver tissue, as well as the elevation of the metabolic activity level. The regulatory mechanism might be related to miR-122-5p.

Aim To develop a ultra-high performance liquid chromatography electrospray-ionization tandem mass spectrometry ( UPLC-MS/MS ) method for the simultaneous determination of salidroside derivative pOBz in rat plasma and brain tissue, and to study the pharmacokinetic profile and penetration of the blood-brain barrier in rats after a single dose intravenous administration of pOBz. Methods SD rats were administered pOBz at a dose of 50 mg • kg