italic>Anoectochilus roxburghii liquid (spray, a hospital preparation of Wu Mengchao Hepatobiliary Hospital of Fujian Medical University) has shown a good clinical treatment effect during the COVID-19 pandemic, but its material basis and mechanism of action are still unclear. In this study, network pharmacology and molecular docking methods were used to predict the molecular mechanism of A. roxburghii liquid against COVID-19, and pharmacodynamic experiments in vitro were conducted to study the interaction between the current targets with clear preventive and therapeutic effects and the key components of A. roxburghii liquid. UPLC-MS and database were used to compare and analyze the active ingredients in the liquid, and 17 potential active ingredients with good drug-like properties were screened by in vivo pharmacokinetics process in SwissADME database. SwissTargetPrediction and GeneCards were searched to find 93 common targets. Cytoscape 3.8.2 software was used to construct the "component-target" network map, and the Metascape platform was used for gene function annotation and pathway enrichment analysis. It was found that the extract could regulate the positive response to external stimuli, inflammatory response, cytokine production and other biological processes by binding the active ingredients such as isorhamnetin, kaempferol, luteolin, quercetin and apigenin to the common targets (NOS3, MPO, MMP3, etc.), and play an anti-COVID-19 role. In the angiotensin-converting enzyme 2 (ACE2) activity inhibition assay, it was found that the stock solution of A. roxburghii liquid (for spray), and the supernatant after removing polysaccharides (mainly containing flavonoids) could to some extent inhibit the activity of ACE2. Crucially, in the experiment of 2019-nCOV-S pseudovirus infecting HEK-293T-ACE2 cells, we found that A. roxburghii liquid may exert anti-COVID-19 effects by blocking the binding of SARS-CoV-S protein to ACE2.

Objective:This study aimed to investigate the correlation between serum chitinase-3 like-protein-1(YKL-40), matrix metalloproteinase-9(MMP-9), and imaging markers in middle-aged and elderly patients with cerebral small vessel disease(CSVD).It also sought to elucidate the mechanism underlying the onset and development of CSVD.Methods:A case-control study was conducted with 130 CSVD patients and 20 age-matched controls admitted to the Department of Neurology of the Second Affiliated Hospital of Zhengzhou University between December 2020 and November 2022.Based on their white matter hyperintensity(WMH)and enlarged perivascular spaces(EPVS)scores, CSVD patients were categorized into mild, moderate, and severe groups.Cerebral microbleeds(CMBs)were classified into non-lacunar, lacunar, non-CMBs, and CMBs groups.Patients' general data were collected, and serum levels of YKL-40 and MMP-9 were measured using ELISA.Results:The results showed 34 cases in the severe WMH group, 35 cases in the EPVS severe group, 90 cases in the group with lacunar and 65 cases in the group with CMBs.Statistically significant differences(both P<0.05)in serum YKL-40 and MMP-9 in WMH severe groups compared to age control group.Statistically significant differences(both P<0.05)in serum YKL-40 and MMP-9 in EPVS severe groups compared to age control group.The increase of serum YKL-40 and MMP-9 levels was an independent risk factor for the severity of WMH( OR=1.25, 95% CI: 0.164-0.289, P<0.05)( OR=1.13, 95% CI: 0.090-0.160, P<0.05)and EPVS( OR=1.05, 95% CI: 0.021-0.076, P<0.05)( OR=1.02, 95% CI: 0.006-0.026, P<0.05).There was no significant different in the serum YKL-40 and MMP-9 levels between lacunar group and non-lacunar group( P>0.05).The serum YKL-40 and MMP-9 levels in the group with CMBs were significantly higher than those in the group without CMBs( P<0.05).The ROC curve showed that the optimal cutoff point of YKL-40 was 0.38, the area under the curve was 0.669(95% CI: 0.569-0.768, P<0.01), the optimal cutoff point of MMP-9 was 0.40, and the area under the curve was 0.746(95% CI: 0.644-0.848, P<0.01). Conclusions:Changes in serum YKL-40 and MMP-9 levels in middle-aged and elderly patients with CSVD were found to be associated with various imaging markers, potentially contributing to the onset and development of CSVD.These findings may aid in early CSVD diagnosis and provide insights for potential interventions.

Atherosclerosis caused by disorders of lipid metabolism is the main pathological basis of atherosclerotic cardiovascular disease.Statins are the cornerstone of lipid-modulating therapy for this type of disease,but in practice there are still some patients with suboptimal lipid management.Proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors have been gradually applied as a new class of lipid-modulating drugs for the treatment in patients with this type of disease,and recent studies have shown that in addition to regulating lipid metabolism,PCSK9 inhibitors also have potential anti-inflammatory and anti-platelet activation effects.This article sorts out the multiple pharmacological mechanisms of action of PCSK9 inhibitors and the current status of clinical research of PCSK9 inhibitors.Besides,it discusses the factors that may affect the efficacy of PCSK9 inhibitors,in order to provide a reference for the safe and rational medication of PCSK9 inhibitors.

The main chemical components of Allii Macrostemonis Bulbus and components in serum were analyzed and identified rapidly and precisely by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)technique in this study.The compounds were identified based on the relative molecular mass,fragmentation ions,and retention time of chromatographic peaks.A total of 36 kinds of chemical components were identified from Allii Macrostemonis Bulbus,including 28 kinds of saponins,3 kinds of amino acids,2 kinds of flavonoids,one kind of organosulfur compound,one kind of nucleoside,and one kind of hormone-lipid compound.In addition,8 kinds of compounds of Allii Macrostemonis Bulbus were identified from the serum.Based on the intersection compounds of which detected in serum and screened out by TCMSP platform database,by using targeted network pharmacology and molecular docking technology,a"drug-component-target-pathway"association network was constructed.Naringenin,quercetin,macrostemonoside E and 25(R)-26-O-β-D-glucopyranosyl-22-hydroxy-5β-furostan-3-O-β-D-glucopyranosyl(1→2)-β-D-glucopyranoside were screened as the main active constituents of Allii Macrostemonis Bulbus in the treatment of hyperlipidemia.In addition,adenosine 5′-monophosphate-activated protein kinase(AMPK),tumor necrosis factor(TNF),vascular endothelial growth factor A(VEGFA)and matrix metallopeptidase 9(MMP9)were the key action targets for Allii Macrostemonis Bulbus in the treatment of hyperlipidemia.Molecular docking was performed using the main pharmacodynamic components and key action targets.The results indicated that all the four active components showed strongly bound to AMPK.This suggested that the regulation of lipid metabolism might be the key mechanism of Allii Macrostemonis Bulbus in antihyperlipidemic effect.This study provided a data reference for the research on the pharmacodynamic components of Allii Macrostemonis Bulbus,and provided a basis for the improvement of quality standard of Allii Macrostemonis Bulbus.

Objective:To analyze the temporal trends of the incidence rate of tuberculosis (TB) in Shaanxi Province and provide a reference for WHO to control the prevalence of TB effectively.Methods:Joinpoint regression was used to analyze the trend of the incidence rate of TB in Shaanxi Province from 2004 to 2022, and the seasonal autoregressive moving average model was used to forecast the incidence rate of TB in Shaanxi Province to 2030.Results:The incidence rate of TB in Shaanxi Province decreased from 90.896/100 000 in 2004 to 35.364/100 000 in 2022, showing a general downward trend (AAPC=-7.72%, P<0.001). From 2014 to 2019, the reduction trend slowed down (APC=-0.69%, P=0.814), of which the largest decline occurred from 2019 to 2022 (APC=-13.26%, P=0.010). The predicted incidence rate of TB in Shaanxi Province from 2020 to 2022 was higher than the reported incidence rate, with the expected incidence rate of 51.342/100 000 in 2022 and 43.468/100 000 in 2030. Conclusion:The incidence rate of TB in Shaanxi Province shows a downward trend from 2004 to 2022, but the decline has shrunk in recent years. It is predicted that the downward trend will continue to slow down by 2030.

Objective To construct an artificial intelligence assisted diagnosis model based on deep learning for dynamically recognizing gastric lesions and their locations under gastroscopy in real time,and to evaluate its ability to detect and recognize gastric lesions and their locations.Methods The gastroscopy videos of 104 patients in our hospital was retrospectively analyzed,and the video frames were manually annotated.The annotated picture frames of lesion category were divided into the training set and the validation set according to the ratio of 8∶2,and the annotated picture frames of location category were divided into the training set and the validation set according to the patient sources at the ratio of 8∶2.These sets were utilized for training and validating the respective models.YoloV4 model was used for the training of lesion recognition,and ResNet152 model was used for the training of location recognition.The accuracy,sensitivity,specificity,positive predictive value,negative predictive value and location recognition accuracy of the auxiliary diagnostic model were evaluated.Results A total of 68 351 image frames were annotated,with 54 872 frames used as the training set,including 41 692 frames for lesion categories and 13 180 frames for location categories.The validation set consisted of 13 479 frames,comprising 10 422 frames for lesion categories and 3 057 frames for location categories.The lesion recognition model achieved an overall accuracy of 98.8%,with a sensitivity of 96.6%,specificity of 99.3%,positive predictive value of 96.3%,and negative predictive value of 99.3% in validation set.Meanwhile,the location recognition model demonstrated an top-5 accuracy of 87.1% .Conclusion The artificial intelligence assisted diagnosis model based on deep learning for real-time dynamic recognition of gastric lesions and their locations under gastroscopy has good ability in lesion detection and location recognition,and has great clinical application prospects.

Objective:To analyze the temporal trends of the incidence rate of tuberculosis (TB) in Shaanxi Province and provide a reference for WHO to control the prevalence of TB effectively.Methods:Joinpoint regression was used to analyze the trend of the incidence rate of TB in Shaanxi Province from 2004 to 2022, and the seasonal autoregressive moving average model was used to forecast the incidence rate of TB in Shaanxi Province to 2030.Results:The incidence rate of TB in Shaanxi Province decreased from 90.896/100 000 in 2004 to 35.364/100 000 in 2022, showing a general downward trend (AAPC=-7.72%, P<0.001). From 2014 to 2019, the reduction trend slowed down (APC=-0.69%, P=0.814), of which the largest decline occurred from 2019 to 2022 (APC=-13.26%, P=0.010). The predicted incidence rate of TB in Shaanxi Province from 2020 to 2022 was higher than the reported incidence rate, with the expected incidence rate of 51.342/100 000 in 2022 and 43.468/100 000 in 2030. Conclusion:The incidence rate of TB in Shaanxi Province shows a downward trend from 2004 to 2022, but the decline has shrunk in recent years. It is predicted that the downward trend will continue to slow down by 2030.

Bile acids not only play an important physiological role in regulating lipid metabolism,but also par-ticipate in the regulation of central nervous system.Numerous studies indicated that abnormal bile acid metabolism is closely related to depression,but the exact mechanism remains unclear.This study summarized the relationship between bile acid metabolism and depression and aimed to provide a new perspective for the study and treatment of depression.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.