BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

With increasing aging， cognitive impairment in elderly coronary heart disease is a "disease group" with high morbidity and mortality in the senior population， which seriously affects the health and quality of life of the elderly. This paper takes the "cardio-cerebral circuit" as the basis of co-morbidity， and under the guidance of the cardio-cerebral homoeopathy， based on the temporal sequential characteristics of the evolution of the disease mechanism of cognitive impairment in elderly coronary heart disease， we construct a “disease-syndrome-phase” prevention and treatment strategy based on the time-sequential characteristics of the pathogenesis of the disease mechanism of "deficiency-blood stasis-toxicity"， from the perspective of pathogenicity of the disease mechanism in time-phase and the spatial multidimensionality of cardio-cerebral homoeopathy. The prevention and treatment strategy of the "disease-syndrome-phase" is constructed from the perspective of the temporal phase of the disease mechanism and the multidimensionality of the space of cardio-cerebral homoeopathy. In the earlier stage， "kidney deficiency and brain emptiness are the foundation"， in the attack stage， "turbid stasis and brain injury are the key"， and in the progression stage， "toxicity and brain damage are the changes". It is emphasized that replenishing the deficiency and benefiting the kidneys to restore the smooth flow of collaterals， eliminating blood stasis and removing turbidity to promote the enrichment of blood， and detoxifying and clearing the heart to tranquilize the spirit and benefit the brain， the spatiotemporal thinking of cognitive impairment of coronary heart disease in the elderly is initially constructed with the spatial dimension to identify the location of the disease， and the temporal dimension to determine the stage of the disease， which will provide a theoretical basis for the spatiotemporal diagnostic and treatments for the heart and brain co-morbidities of TCM.

OBJECTIVE To explore the potential geographic distribution of Pinellia Ternata (Thunb.) Breit. in Gansu province, clarify its habitat requirements, and provide a theoretical basis for rational cultivation. METHODS Based on 100 geographic distribution points of Pinellia Ternata (Thunb.) Breit. and 39 environmental variables (including 19 bioclimatic variables, 17 soil variables and 3 topographic variables), the maximum entropy model(MaxEnt) and ArcGIS geographic information system software were used to make the habitat suitable for its evaluation and classification of suitable areas, the result of Jackknife test was used to evaluate the environmental variables that affect the habitat of Pinellia Ternata (Thunb.) Breit., the area under the ROC curve(AUC) was used to evaluate the degree of reliability of the prediction results. RESULTS The AUC was 0.993, indicating that the prediction results of the MaxEnt model were reliable. Monthly average daily temperature difference, isotherm, standard deviation of seasonal variation of temperature, annual precipitation, the wettest month precipitation, the driest month precipitation, the driest season precipitation, the coldest season precipitation and altitude were the main environmental variables affecting the growth of Pinellia Ternata (Thunb.) Breit.. The suitable areas for Pinellia Ternata (Thunb.) Breit. in Gansu were mainly concentrated in Longnan, Tianshui and Pingliang, where the areas of high, medium and low suitable areas were 16 180.4, 15 413.96, 21 204.84 km2, respectively. CONCLUSION The research results can provide a theoretical reference for the protection and standardized cultivation of Pinellia Ternata (Thunb.) Breit. resources.

Objective:To investigate the effectiveness and safety of ultrasound-guided endovascular therapy for autogenous arteriovenous fistula (AVF) thrombosis.Methods:It was a single-center retrospective cohort study. Data of patients undergoing ultrasound-guided intravascular therapy due to AVF thrombosis in the First Hospital of Hebei Medical University from August 2018 to June 2021 were analyzed. According to different surgical procedures, the patients were divided into two groups. Patients treated with percutaneous transluminal angioplasty (PTA) + drilling thrombectomy were in group A, and patients treated with PTA only were in group B. After 1 year of follow-up, the surgical technique success rate, primary patency rate, secondary patency rate and complications were compared between the two groups.Results:A total of 152 patients were enrolled, including 74 in group A and 78 in group B. There were no significant differences in gender, age, proportion of patients with diabetes and hypertension, and thrombosis time of AVF between the two groups (all P>0.05). Compared with group B, the diameter and length of thrombus in group A were larger [13.0(9.0, 16.0) mm vs. 6.0(5.0, 6.5) mm, Z=-9.362, P<0.001; 12(8, 15) cm vs. 3(3, 4) cm, Z=-10.061, P<0.001], and the establishment time of AVF was longer [5(2, 7) years vs. 2(1, 5) years, Z=-2.698, P=0.007]. Among the overall patients, the success rate of surgery was 96.7% (147/152), and the success rate of surgery was 95.9% (71/74) in group A and 97.4% (76/78) in group B respectively, with no statistical difference ( χ2=0.004, P=0.952). Kaplan-Meier survival analysis showed that, overall, the primary patency rate at 3rd, 6th and 12th month after operation was 87.1%, 71.4% and 56.6%, and the secondary patency rate was 97.1%, 96.4% and 94.1%, respectively. The primary patency rate of group A at 3rd, 6th and 12th month was 82.4%, 66.7% and 53.6%, and the secondary patency rate was 95.7%, 94.2% and 89.7%, respectively. The primary patency rate of group B at 3rd, 6th and 12th month was 91.5%, 73.2% and 59.7%, and the secondary patency rate was 98.6%, 98.6% and 98.5%, respectively. There was no significant difference in the primary and secondary patency rate between group A and group B at 3rd, 6th and 12th month (all P>0.05). The duration of operation in group A was longer than that in group B [2.0(1.9, 2.0) h vs. 2.0(1.0, 2.0) h, Z=-5.181, P<0.001], but no serious complications occurred in both groups. Conclusion:The two surgical methods are effective, safe and reliable in the treatment of AVF thrombosis, and have high clinical application value.

Objective:To observe the clinical efficacy of pressing-kneading manipulation combined with herb-insulated moxibustion at Shuidao(ST28)for postpartum urinary retention after labor analgesia and its effect on bladder urination function. Methods:A total of 154 patients with postpartum urinary retention after labor analgesia were randomly divided into a Western medication group and a herb-insulated moxibustion group,with 77 cases in each group.In the Western medication group,neostigmine sulfate was injected into Zusanli(ST36).In the herb-insulated moxibustion group,after pressing-kneading manipulation at Shuidao(ST28),herb-insulated moxibustion was applied to Shuidao(ST28)with self-made Tong Quan San.Both groups were treated once,and the clinical efficacy was evaluated 5 h after treatment.The first urination time,first urination volume,average urinary flow rate,bladder residual urine volume,hospitalization days,and costs were recorded. Results:The total effective rate and markedly effective rate of the herb-insulated moxibustion group were higher than those of the Western medication group(P<0.05),the time to the first urination and residual urine volume in the bladder of the herb-insulated moxibustion group were shorter or smaller than those of the Western medication group(P<0.01),the first urination volume and average urine flow rate of the herb-insulated moxibustion group were larger than those of the Western medication group(P<0.01).There were no significant differences in the hospitalization days and costs between the two groups(P>0.05). Conclusion:Pressing-kneading manipulation combined with herb-insulated moxibustion at Shuidao(ST28)can effectively treat postpartum urinary retention after labor analgesia and improve bladder urination function.

Objective To investigate the characteristics of electrocardiogram changes during nocturnal asymptomatic hypoglycemia in type 2 diabetes mellitus(T2DM)patients and early diagnosis of cardiac autonomic neuropathy(CAN).Methods A total of 150 patients with T2DM who were admitted to our hospital from June 2015 to June 2022 were retrospectively selected and given 72 h dynamic blood glucose and dynamic electrocardiogram monitoring.According to whether asymptomatic hypoglycemia occurred at night,they were divided into hypoglycemia group(n=62)and non-hypoglycemia group(n=88).According to the Ewing experiment,150 T2DM patients with T2DM were divided into T2DM group(n=90)and CAN group(n=60).Results Compared with the non hypoglycemic group,the hypoglycemic group had an increase in DM duration,LF/HF(P<0.05),HbA1c,average blood glucose,collected heart rate deceleration force(DC),QT dispersion(QTD),end of peak T value(Tp-e),Tp-e/QT,percentage of beats with a difference of more than 50 ms between adjacent normal RR intervals(pNN50),root mean square difference between adjacent normal RR intervals(rMSSD),standard deviation of 24-hour normal sinus RR interval(SDNN),and standard deviation of mean normal RR interval every 5 minutes(SDANN)and the average heart rate decreased within 24 hours decreased(P<0.05).Logistic regression analysis showed that the duration of DM was a risk factor for CAN in T2DM patients,and DC,QTD,and pNN50 were protective factors for CAN in T2DM patients.The characteristic curve analysis of the participants showed that the area under the curve for predicting CAN was 0.811,0.842,0.786,0.801,and 0.886 for the DM duration,DC,QTD and pNN50 respectively.The combined diagnostic performance of these four items was the best.After internal verification,it was found that the model has good discrimination and accuracy.Conclusion T2DM patients with nocturnal asymptomatic hypoglycemia may exhibit elevated,ECG LF/HF and decreased DC,QTD,Tp-e,Tp-e/QT,pNN50,rMSSD,SDNN,SDANN,and 24-hour average heart rate decrease;DM duration,DC,QTD and pNN50 can serve as effective indicators for early diagnosis of CAN in T2DM patients.

Objective:To explore the diagnostic value of improved 18F-prostate specific membrane antigen (PSMA)-1007 PET-CT score (referred to as PSMA score) and multi parameter magnetic resonance imaging (mpMRI) prostate imaging reporting and data system (PI-RADS) score (referred to as PI-RADS score) for primary prostate cancer (PCa). Methods:A retrospective case series study was conducted. The imaging and clinical data of 134 suspected PCa patients underwent 18F-PSMA-1007 PET-CT and mpMRI examinations at Shanxi Province Cancer Hospital from July 2018 to May 2023 were collected. Pathological diagnosis showed 92 cases of PCa and 42 cases of benign prostatic lesions. The clinical and imaging parameters, as well as the distribution of patients with two scores, were compared between the two groups. The blind diagnosis of benign and malignant lesions was made based on the improved PSMA score (dividing 1 point into 1a and 1b points, 1b, 2 and 3 points were diagnosed as PCa), PI-RADS score (3, 4 and 5 points were diagnosed as PCa) and the combination of the two (diagnosed as PCa when either PSMA score ≥ 1b point or PI-RADS score ≥ 4 points was met). The indicators of the diagnostic efficiency of PSMA score, PI-RADS score and the combination of the two for PCa were calculated. Using pathological results as the gold standard, the receiver operating characteristic (ROC) curve of PSMA score, PI-RADS score and the combination of the two for diagnosing PCa was drawn, and the diagnostic efficiency of the 3 methods was analyzed. Results:The age, serum prostate-specific antigen, and maximum standard uptake value of PET-CT in the PCa group were higher than those in the benign prostatic lesion group, and the differences were statistically significant (all P < 0.05). The sensitivity, specificity, accuracy, false negative rate, false positive rate, positive predictive value, and negative predictive value of PSMA score for diagnosing PCa were 91.30% (84/92), 80.95% (34/42), 88.06% (118/134), 8.70% (8/92), 19.05% (8/42), 91.30% (84/92), and 80.95% (34/42), respectively; those of PI-RADS score were 93.48% (86/92), 61.90% (26/42), 83.58% (112/134), 61.90% (26/42), 38.10% (16/42), 84.31% (86/102), and 81.25% (26/32), respectively; those of the combination of the two were 97.83% (90/92), 88.10% (37/42), 94.78% (127/134), 2.17% (2/92), 11.90% (5/42), 94.74% (90/95), and 94.87% (37/39), respectively. The differences in specificity, accuracy, false negative rate, and false positive rate among the 3 methods were statistically significant (all P < 0.05). ROC curve analysis showed that the area under the curve of PSMA score, PI-RADS score and the combination of the two for diagnosing PCa were 0.930 (95% CI: 0.872-0.967), 0.935 (95% CI: 0.826-0.939) and 0.959 (95% CI: 0.910-0.986), respectively, and the differences between each two methods were statistically significant (all P < 0.05); the sensitivity of PSMA score, PI-RADS score and the combination of the two was 90.11%, 89.13% and 98.09%, and the specificity was 90.48%, 90.48% and 92.09%. Conclusions:Compared with the PI-RADS score, the improved PSMA score can improve the specificity and accuracy of PCa diagnosis, and decrease the false negative and false positive rates; the diagnostic efficiency of the combination of the two is superior.

ObjectiveTo investigate the relative content changes of differential metabolites and reducing sugars during the processing process of Rehmanniae Radix Praeparata （RRP） processed with Amomi Fructus （AF） and Citri Reticulatae Pericarpium （CRP）， and to lay the foundation for revealing the processing principle of this characteristic variety. MethodThe samples of the 0-54 h processing process of RRP processed with AF and CRP were taken as the research object， and their secondary metabolites were detected by ultra performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）. The 0.1% formic acid aqueous solution （A）-acetonitrile （B） was used as the mobile phase for gradient elution （0-1 min， 1%-3%B； 1-10 min， 3%-9%B； 10-15 min， 9%-12%B； 15-22 min， 12%-18%B； 22-31 min， 18%-24%B； 31-35 min， 24%-100%B； 35-36 min， 100%-5%B； 36-40 min， 5%-1%B； 40-45 min， 1%B）， column temperature was 40 ℃， injection volume was 3 μL， flow rate was 0.3 mL·min^-1. Electrospray ionization （ESI） was used to scan and collect MS data in the negative ion mode， the scanning range was m/z 50-1 250. Data analysis was carried out using PeakView 1.2 software， and the chemical composition of RRP processed with AF and CRP was identified by combining the literature information and chemical composition databases. The MS data were normalized by MarkerView 1.2， and then the multivariate statistical analysis was applied to screen the differential metabolites， and the changes of the relative contents of the differential metabolites with different processing times was analyzed， finally， correlation analysis was performed between the differential metabolites， the change of the reducing sugar content was combined to determine the most suitable processing time of RRP processed with AF and CRP. ResultA total of 121 compounds were identified from RRP processed with AF and CRP at different processing times， and 12 differential metabolites were screened out by multivariate statistical analysis， including catalpol， hesperidin， isoacteoside， acteoside， narirutin， echinacoside， isomartynoside， decaffeoylacteoside， 6-O-E-feruloylajugol， dihydroxy-7-O-neohesperidin， jionoside D， and rehmapicroside. With the prolongation of processing time， the relative contents of these 12 differential metabolites and reducing sugars changed slightly at 52-54 h. ConclusionUPLC-Q-TOF-MS can comprehensively and accurately identify the chemical constituents of RRP processed with AF and CRP at different processing times， and the suitable processing time of 52-54 h is determined according to the content changes of different metabolites and reducing sugars， which provides a basis for revealing the scientific connotation of the processing principle of this variety.

By reviewing the relevant literature of ancient herbal works and modern codices， this paper sorted out the historical evolution and developmental venation of processing of Notoginseng Radix et Rhizoma. On this basis， the modern research of processed products of Notoginseng Radix et Rhizoma was used as the breakthrough point to analyze the literature in terms of processing technology， chemical composition changes and changes in pharmacological effects before and after processing. According to the research status of processing of Notoginseng Radix et Rhizoma， some existing problems were analyzed in this paper， such as not many ancient processing methods used in modern time， lack of standardized research on processing technology. And saponins， polysaccharides， amino acids， flavonoids and other chemical components in Notoginseng Radix et Rhizoma may change to different degrees before and after processing， which was the main reason for the difference of efficacy before and after processing. However， the current research on the pharmacological effects of Notoginseng Radix et Rhizoma mainly focuses on raw products， resulting in a lack of in-depth research on the transformation mechanism of Notoginseng Radix et Rhizoma in processing difference， and the scientific connotation of "Shengxiao Shubu" has not been clearly elaborated， which is not conducive to the standardized clinical use of drugs. Therefore， it is necessary to further analyze the material basis of Notoginseng Radix et Rhizoma and its processed products， and to explore the change rule of chemical components before and after processing and its correlation with pharmacodynamic activity， so as to clarify the processing mechanism for providing scientific basis for its standardized processing， quality control and clinical rational use.

The high-performance liquid hromatography-quadrupole-electrostatic field orbital well high-resolution mass spectrometry method was developed for the analysis of p-methoxymethamphetamine(PMMA)and its metabolites in rabbit blood.Hypersil Gold aQ(2.1 mm×100 mm,1.9 μm)was used as the chromatographic column.The mobile phase was gradient elution with 0.1%formic acid aqueous solution(A)and 0.1%formic acid acetonitrile(B)at a flow rate of 0.3 ml/min.Electrospray ionization(ESI)with positive and negative mode scanning was used to determine p-methoxymethamphetamine and its metabolites based on excimer and secondary fragment ions.PMMA and its metabolites were characterized by high-performance liquid chromatography-high resolution mass spectrometry,which lays a foundation for the study of its pharmacodynamic substance and prevention.