OBJECTIVE To predict and validate the potential mechanisms of Kaixinsan （KXS） in ameliorating neuroinflammation in Alzheimer’s disease （AD）. METHODS Network pharmacology was employed to identify core anti- inflammatory components and key inflammatory targets of KXS for AD. Gene ontology （GO） functional annotation， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment， and molecular docking were performed. Based on these findings， male SD rats were used to establish an AD model via chronic D-galactose induction. The effects of KXS on AD rats were evaluated， including quantitative behavioral score， learning and memory parameters （escape latency， platform crossings， platform quadrant distance and time）， organ indexes （heart， liver， spleen， thymus）， histopathological alterations in the hippocampus， and expressions of inflammation-related pathway proteins and their upstream/downstream regulators. RESULTS Core anti-inflammatory components of KXS for AD included gomisin B， panaxytriol， gomisin A， enhydrin， vulgarin and panaxydol， while key inflammatory targets involved nuclear factor-kappa B subunit 1（ NFKB1）， nuclear factor-κB p65（ NF-κB p65）， interleukin-1β（ IL- 1β）， IL-6， Toll-like receptor 4 （TLR4）， tumor necrosis factor， nucleotide-binding domain leucine-rich repeat and pyrin domain- containing receptor 3 （NLRP3） and caspase-1 （CASP1）. GO and KEGG pathway enrichment involved inflammatory response， phosphorylation and the NF-κB signaling pathway. Molecular docking confirmed strong binding affinities between core components and key targets. Animal experiments demonstrated that， compared to the model group， KXS significantly alleviated histopathological damage （e.g.， neuronal shrinkage， reduced Nissl bodies in hippocampal CA1， CA3， and DG regions）， increased organ indexes （except for liver index） and Nissl-stained positive cells， improved learning and memory performance， and reduced behavioral scores （at the 8 and 12 weeks of the experiment） and protein expression of NF- κB p65， phosphorylated NF- κB p65， TLR4， NLRP3， CASP1 and IL-1β. CONCLUSIONS KXS effectively mitigates neuroinflammation， reduces hippocampal neuronal injury， and enhances learning and memory ability in AD rats， potentially through suppressing the NF-κB signaling pathway and its upstream/ downstream regulators.

Objective To explore the pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Methods The pharmacological model of hyperuricemia was established.The chemical components in vivo and in vitro of Simiao Wan were analyzed by UPLC-Q-Exactive-MS.Based on the components absorbed in blood,the"active ingredient-target-pathway"network of Simiao Wan for regulating hyperuricemia and gout was constructed by network pharmacology method.The key ingredients were used for molecular docking with key targets[uricogenase(XDH),uric acid transporter(ABCG2,GLUT9,OAT1,URAT1)and inflammatory targets(PTGS2,TLR2,TLR4)]of hyperuricemia and gout.Finally,experimental verification was conducted according to the results of molecular docking.Our aim is to identify the key pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Results Eighty-nine components of Simiao Wan were identified by UPLC-Q-Exactive-MS analysis,including 74 components absorbed in blood,which were confirmed as candidate ingredients.Network pharmacology was used to constructed"components absorbed in blood-target-pathway"network,and components absorbed in blood were matched with 116 targets of hyperuricemia and 173 targets of gout.It is involved in the regulation of biological processes,such as glucose and lipid metabolism,oxidative stress,inflammatory response,ERK1 and ERK2 cascade,MAPK cascade,PI3K signal transduction.Moreover,Simiao Wan plays a role in regulating the network of hyperuricemia and gout through regulating blood lipids and atherosclerosis,apoptosis,AGE-RAGE,TNF,PI3K-Akt,MAPK,TLRs,JAK-STAT,NF-κB and other signaling pathways.Molecular docking studies showed that berberine,phellodendrine,magnoflorine,jatrorrhizine,palmatine,obacunone,limonin,atractylodin,taxifolin,atractylenolide Ⅲ and β-ecdysterone had good affinity with uric acid synthase,uric acid transporter and inflammatory targets.Western Blot test showed that taxifolin negatively regulates the expression of URAT1.The above-mentioned compounds were the main pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Conclusion This article describes the main pharmacodynamic substances of Simiao Wan in the regulation of hyperuricemia and gout,which can provides a scientific basis for the clinical application,improvement in quality evaluation and standard of Simiao Wan.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly used as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring no actionable mutations; however, data on their efficacy among patients presenting with intracranial lesions are limited. This study aimed to explore the efficacy and safety of ICIs combined with chemotherapy in advanced NSCLC patients with measurable brain metastasis at initial diagnosis. METHODS: Our study retrospectively analyzed clinical data of a total of 211 patients diagnosed with driver gene mutation-negative advanced NSCLC with measurable, asymptomatic brain metastasis at baseline from Hunan Cancer Hospital between January 1, 2019 and September 30, 2021. The patients were stratified into two groups according to the first-line treatment regimen received: ICI combined with chemotherapy ( n = 102) or chemotherapy ( n = 109). Systemic and intracranial objective response rates (ORRs) and progression-free survival (PFS) were analyzed. Adverse events were also compared between the groups. RESULTS: Compared with the chemotherapy-based regimen, the ICI-containing regimen was associated with a significantly higher intracranial (44.1% [45/102] vs . 28.4% [31/109], χ2 = 5.620, P = 0.013) and systemic (49.0% [50/102] vs . 33.9% [37/109], χ2 = 4.942, P = 0.019) ORRs and longer intracranial (11.0 months vs . 7.0 months, P <0.001) and systemic (9.0 months vs . 5.0 months, P <0.001) PFS. Multivariable analysis consistently revealed an independent association between receiving ICI plus platinum-based chemotherapy as a first-line regimen and prolonged intracranial PFS (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.37-0.73, P <0.001) and systemic PFS (HR = 0.48, 95% CI: 0.35-0.66, P <0.001). No unexpected serious adverse effects were observed. CONCLUSION: Our study provides real-world clinical evidence that ICI combined with chemotherapy is a promising first-line treatment option for driver gene mutation-negative advanced NSCLC patients who present with brain metastasis at initial diagnosis. CLINICAL TRIAL REGISTRATION https://www.clinicaltrials.gov/ , OMESIA, NCT05129202.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies ; Brain Neoplasms/genetics*

Objective:To investigate the effect of automated nested multiplex PCR system in the detection of children with severe community-acquired pneumonia(CAP), and identify the pathogenic infection of the children with severe CAP in Foshan.Methods:Children with severe CAP, who were admitted to the PICU at Foshan First People′s Hospital from January 2016 to December 2018, were enrolled in the analysis.Nasopharyngeal secretions were collected.And automated nested multiplex PCR was used to detect adenovirus, coronavirus (HKUl type, NL63 type, 229E type, 0C43 type), human metapneumovirus, influenza A virus (H1 subtype, H1-2009 subtype, H3 subtype), influenza B virus, parainfluenza virus (type 1, type 2, type 3, type 4), respiratory syncytial virus, Bacillus pertussis, Chlamydia pneumoniae and Mycoplasma pneumonia.Results:Among the 290 specimens detected by the automated nested multiplex PCR, 246(84.83%) were positive.There were 166 positive samples for a single pathogen, 60 positive samples for two pathogens, 17 positive samples for three pathogens, and three positive samples for four pathogens.Among the virus-positive cases, respiratory syncytial virus was the most common pathogen in children younger than 6 months(62.39%, 73/117). The most common pathogen was human rhinovirus/enterovirus(43.48%, 20/46) from seven months to one year old.Adenovirus(37.50%, 18/48) was the most common pathogen among children aged one to three years old.Rhinovirus/enterovirus(35.00%, 7/20) was the most common pathogen among children aged three to six years old.The most common pathogen in children over six years old was influenza virus(46.67%, 7/15). The adenovirus detection rate was highest in May, the syncytial virus detection rate was highest in August, and the influenza virus detection rate was highest in July.Mycoplasma pneumoniae and pertussis were distributed throughout the year.Conclusion:The automated nested multiplex PCR system can detect multiple pathogens efficiently, quickly and accurately; the common pathogens of severe CAP are diverse in different age groups; the epidemic season of common pathogens is unique in different regions due to different climates.

Objective To investigate the distribution characteristics and changing tendency of urinary tract stones.Methods From January 2011 to May 2017,clinical data of 15 269 patients treated in our center was retrospectively reviewed.The stone components were detected by the automatic stone infrared spectroscopy system and the predominant components were recorded.There were 9 019 male patients and 6 250 female patients.The patients were divided into four groups according to their age,including group A ≤ 18 years;group B 19-40 years;group C 41-60 years;and group D ＞ 60 years.Compared the distribution characteristics of urinary tract stones of patient in different groups of sex,age and calendar year.Results Calcium oxalate stones were more prevalent in males than females [6 221 (69.0％)vs.3 582 (57.3％),P ＜ 0.001],but calcium phosphate stones [210 (3.4％) vs.210 (2.3％)],magnesium ammonium phosphate stones [230(3.7％) vs.165 (1.8％)] and carbonate apatite stones [1 328 (21.3％) vs.1 030 (11.4％)] were more common in females than males (P ＜ 0.001,respectively).The proportion of uric acid stones in group D [679(20.7％)] was higher than that in group A [23(9.1％)],group B[260(7.9％)],group C [1 163 (13.8％)] (P ＜0.001,respectively).The peak of carbonate apatite stones was showed in group B [652(19.7％)] (P＜0.001,respectively).Ammonium urate stones [9(3.5％)] and cystine stones [36 (14.2％)] were more frequent in group A(P ＜0.001,respectively).In adults,the percentage of uric acid stones increased with age,such as group B [260(7.9％)],group C [1 163(13.8％)],group D [679 (20.7％)].And the carbonated apatite stones decreased with age,such as group B [652 (19.7％)],group C [1 270(15.1％)],group D [416(12.7％)] (P ＜0.001,respectively).Further analysis showed the proportion of calc ium oxalate (OR =0.944,95 ％ CI 0.927-0.962,P ＜ 0.001),ammonium urate stones (OR =0.854,95％ CI 0.742-0.982,P =0.027) decreased,while calcium phosphate (OR =1.192,95％ CI 1.127-1.261,P ＜0.001),uric acid (OR =1.042,95％ CI 1.015-1.069,P =0.002) and ammonium magnesium phosphate (OR =1.078,95％ CI 1.019-1.141,P =0.009) stones increased with time.Conclusions The distribution of stones was different in genders and age.Calcium oxalate stones were more common in male patients,while ammonium magnesium phosphate and carbonate apatite stones were more common in female patients.Uric acid stones were more frequent in patients older than 60,while carbonate apatite were more frequent in the 19-40 age group.The proportion of calcium oxalate and ammonium urate stones showed a downward trend,whereas calcium phosphate,uric acid and magnesium ammonium phosphate stones increased with time.

Objective To compare measurements of dual-energy CT iodine map parameters and liver perfusion CT parameters in patients with focal liver lesions using a third-generation dual-source CT scanner. Methods Between November 2015 and August 2016,33 patients with non-cystic focal lesions of liver were enrolled in this study. CT examinations were performed with a third-generation dual-source CT. The study CT protocol included a perfusion CT and dual-energy arterial and portal venous scans,with a time interval of 15 minutes. Iodine attenuation was measured at five region of interests including areas of high,medium,and low density within the lesion,as well as right and left liver parenchyma from the iodine map,while arterial liver perfusion (ALP),portal venous liver perfusion (PVP),and hepatic perfusion index (HPI) at the same location were measured from perfusion CT. The Pearson product-moment correlation coefficient was used to evaluate the relationship between iodine attenuation and perfusion parameters. Results The iodine attenuation at arterial phase showed significant intra-individual correlation with ALP (r=0.812,95% CI=0.728-0.885,P<0.001)and PVP (r=-0.209,95% CI=-0.323--0.073,P=0.007),but not significantly correlated with HPI (r=0.058,95% CI=0.046-0.498,P=0.461). The iodine attenuation at portal venous phase showed significant correlation with PVP (r=0.214,95% CI=0.072-0.361,P=0.005) but not with HPI(r=0.036,95% CI=-0.002-0.242,P=0.649). The mean effective dose of arterial phase and portal venous phase of dual-energy CT together [(3.53±1.17)mSv] was significantly lower than that of the perfusion CT [(14.53±0.45)mSv](t=25.212,P<0.001). Conclusion Iodine attenuation from arterial phase of dual energy CT demonstrates significant correlation with ALP and PVP,and iodine attenuation from portal venous phase demonstrates significant correlation with PVP.
Contrast Media ; Humans ; Iodine ; Liver ; diagnostic imaging ; pathology ; Perfusion ; Portal Vein ; Tomography, X-Ray Computed ; methods

Objective To investigate the SCCmec types of clinically isolated methicillin‐resistant Staphylococcus epidermidis (M RSE) .Methods Eighty‐four strains of clinically isolated Staphylococcus epidermidis identified by the fully automatic microbio‐logical identification system were collected and performed the MRSE identification by PCR for amplifying esp and mecA genes and SCCmec typing .Its distribution characteristics were analyzed .Results Esp gene was amplified in 84 strains and the detection rate of mecA was 76 .19% (64/84) ,in which the MRSE detection rates in blood ,sputum ,urine and wound secretion were 76 .8% , 68 .8% ,100% and 71 .4% respectively .The multiple PCR amplification displayed that among 64 strains of MRSE ,19 strains were SCCmec simple type ,in which 19 strains were SCCmec type Ⅰ and 3 strains were SCCmec type Ⅲ ;42 strains were SCCmec mixed type ,in which 2 strains were SCCmec mixed type Ⅰ and Ⅱ ,14 strains were SCCmec mixed type Ⅰ and Ⅲ ,12 strains were SCCmec mixed type Ⅰ ,Ⅱ and Ⅲ ,5 strains were SCCmec mixed type Ⅱ and Ⅲ ,a strains were and SCCmec mixed type Ⅲ and Ⅳ .Conclu‐sion The SCCmec type in clinically isolated MRSE shows obvious diversity and its majority is SCCmec mixed type .

Objective To construct mutant strains of methicillin resistant Staphylococcus epidermi-dis (MRSE) with psm-mec gene deletion and to investigate the function of psm-mec gene.Methods The drug sensitivity test and DNA sequence analysis were performed to screen out the tetracycline and chloram -phenicol sensitive clinical strains of MRSE , whose upstream and downstream sequences of psm-mec gene were identical to those of the Staphylococcus epidermidis reference strain RP62A.The recombinant plasmid pBT2-Δpsm-mec was constructed by using the fusion PCR and a temperature sensitive shuttle plasmid .After being identified , the plasmid was transformed into the Staphylococcus aureus RN4220 strain by electropora-tion, and then transformed into the selected clinical isolates of MRSE .The mutant strains of MRSE with psm-mec deletion were screened out and identified after homologous recombination .The differences in biofilm formation between the mutant and wild-type strains were analyzed for further elucidation the relationships be-tween the psm-mec gene and biofilm formation in MRSE strains .Results Three clinical MRSE isolates for the construction of mutant strains with psm-mec gene deletion were screened out and identified by using drug sensitivity test and sequence alignment analysis .The mutants constructed via homogenous recombination were screened out and identified .Compared with the corresponding wild-type strains, the three mutants with psm-mec gene deletion showed significantly decreased ability of biofilm formation , demonstrating that the psm-mec genes strains induced the biofilm formation of MRSE .Conclusion The Δpsm-mec mutant strains were successfully constructed .The psm-mec gene played an important role in the biofilm formation of Staphy-lococcus epidermdis.

Objective To investigate the genetic location of SCCmec-associated psm-mec in Staphylococcus hominis isolated from blood culture,and to lay a foundation for further functional studies of psm-mec in Staphylococcus hominis.Methods 25 strains of Staphylococcus hominis isolated from positive blood culture were collected.mecA and psm-mec gene were amplified by PCR,and the SCCmec types were determined by the results of multiplex PCR assay.For analyzing the genetic location characteristic of psm-mec in SCCmec,three pair special PCR primers were used to measure mecR1/psm-mec,psm-mec/xylR and fudoh respectively.Results There were 21 strains of methicillin-resistant Staphylococcus hominis and 4 strains of methicillin-sensitive Staphylococcus hominis. The positive rate of psm-mec gene in methicillin-resistant Staphylococcus hominis was 47.6%,and no psm-mec gene was found in methicillin-sensitive Staphylococcus hominis.Among psm-mec positive strains,2 strains belonged to SCCmecⅢ,5 strains belonged to SCCmecⅢ-like,and 3 strains belonged to new SCCmec types.All of the 10 psm-mec positive strains were mecR1/psm-mec,psm-mec/xylR and fudoh gene positive.Conclusion SCCmec-associated psm-mec extensively exists in methicillin-resistant Staphylococ-cus hominis isolated from positive blood culture,which distributes mainly in typical SCCmecⅢ,SCCmecⅢ-like and new SCCmec types and locates between mecR1 and xylR gene.

Objective To investigate the influence of application of local anesthesia with lidocaine on bronchial lavage fluid (BLF) pseudomonas aeruginosa culture and drug sensitivity in cases with lung infection .Methods Two hundred and seventy speci-men of BLF were collected from 135 patients with infection of lung .And BLF were collected directly from right-broncho in control group ,and from left-broncho in lidocaine group .The outcome of pseudomonas aeruginosa culture and drug sensitivity were com-pared in the two groups .Results Fourty-two cases were postitive in BLF pseudomonas aeruginosa culture in the control group ,and 40 cases were postitive in lidocaine group .The positive rates were 31 .11% and 29 .63% ,respectively .There were no significance between the two groups (P<0 .001) .Compared with the control group ,the sensitive strains of pseudomonas aeruginosa were obvi-ously less and the drug tolerance strains were much more in lidocaine group for Ciprofloxacin and Levofloxacin (P<0 .05) .Howev-er ,there were no influence for drugs such as Piperacillin/Tazobactam and Ceftazidime ,etc .Conclusion 2% lidocaine has no influ-ence on the outcome of BLF pseudomonas aeruginosa culture .But it may reduce the drug sensitivity of Ciprofloxacin and Levofloxa-cin in cases with infection of lung .