OBJECTIVE To investigate the mechanism by which Qiaobai cold compress solution （QBCS） improves acne vulgaris （AV） based on transcriptomics and animal experiments. METHODS Rats were randomly divided into a blank control group （ n ＝6） and a modeling group （ n ＝30）. AV models were established in the modeling group by topical application of oleic acid to the inner surface of both ears， combined with subcutaneous injection of Cutibacterium acnes suspension into the auricle. Successfully modeled rats were further divided into the model group， positive control group （Tretinoin cream， 0.045 g/kg）， and QBCS low-， medium-， high-dose groups [3.55， 7.11， 14.22 g/kg （calculated by the amount of crude drug） ] ， with 6 rats in each group. Rats in each d rug group were treated with the corresponding drugs once daily for 14 consecutive days. After the final administration， changes in the appearance of the ears and histopathological changes in the ear tissues were observed， and serum levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β， were measured. Auricular tissues from the blank control group， model group and QBCS medium-dose group were collected for transcriptome sequencing. Differential expressed genes （DEGs） were screened and subjected to Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis， followed by validation using real-time quantitative polymerase chain reaction and Western blot assay. RESULTS Compared with the model group， rats in all QBCS groups showed alleviated auricular acne symptoms， with reduced epidermal thickening， sebaceous gland hyperplasia， and inflammatory cell infiltration. Serum levels of TNF-α （except for the QBCS low-dose group）， IL-6 （except for the QBCS low-dose group） and IL-1β were significantly decreased （ P ＜0.05）. A total of 590 DEGs were identified （blank control group vs. model group）， and 596 DEGs were identified （model group vs. QBCS medium-dose group）. Above DEGs （blank control group vs. model group） were mainly enriched in Toll-like receptor （TLR） and nuclear factor-kappa B （NF-κB） signaling pathways， etc. Validation experiments showed that， compared with model group， low-， medium- and high-dose of QBCS reduced， to varying degrees， the mRNA expression of TNF-α， TLR2， interferon-γ and CXC chemokine ligand 8 in the auricular tissues of AV rats， increased the mRNA expression of peroxisome-proliferator-activated receptor gamma and tumor protein 53， and inhibited the phosphorylation of NF-κB p65 protein as well as the expressions of TLR2 and myeloid differentiation primary response protein 88（MyD88） （ P ＜0.05）. CONCLUSIONS QBCS can alleviate auricular inflammation and skin lesions in AV rats. This effect may be related to inhibition of the TLR/MyD88/NF-κB signaling pathway， thereby suppressing the expression of downstream inflammatory factors such as TNF-α.

ObjectiveThis study aims to explore the potential of different orders of magnitude single-nucleotide polymorphism (SNP) locus combinations for predicting distant kinship relationships. A high-density SNP locus set was constructed, and a comprehensive assessment of its inference capability was conducted. MethodsFirstly, we selected three commercial chip panels, CGA (Chinese genotyping array, Illumina), GSA (Global screening array, Illumina), Affy (23MF_V2 high-density SNP array, Affymetrix) and merged them after quality control, forming a high-density SNP locus panel(1 180 k). Secondly, we selected 161 samples and collected their peripheral blood samples by using whole-genome sequencing technology. Within this sample population, the levels of kinship relationships fully covered the range from level 1 to level 9, and the number of kinship pairs at each level was consistently maintained at over 50 pairs. From 161 samples data of whole-genome sequencing, the 1 180 k locus set was extracted, which is referred to as the high-density SNP locus set in the following text. The kinship inference was conducted using the identity-by-descent (IBD) algorithm with the selected optimal parameters. To comprehensively evaluate the performance of the high-density SNP locus set in kinship inference, we compared it with the three commercial chip panels, the intersection of these three chip loci, and the control sets constructed by randomly reducing the number of the high-density SNP locus set. Based on the changes in the IBD lengths, as well as the dynamic trends in prediction accuracy, we conducted a scientific assessment of the kinship inference capability of the high-density SNP locus set. ResultsAfter screening, a set of 1 184 334 autosomal SNPs was obtained. During the process of screening the optimal IBD length threshold, the result revealed that 0 cM, 1 cM, and 2 cM all demonstrated good applicability. However, to avoid the issue of a large amount of redundant information caused by setting a too low IBD length threshold, this study ultimately selected 2 cM as the optimal threshold. Compared with the average results of three chip panels, the high-density SNP locus set increased the total IBD length and the average IBD length across levels 1-9; the accuracy of the confidence interval for level 8 was 70.97%, which represented a 3.50% improvement; the average confidence interval accuracy for levels 1-8 was 91.39%, representing a 1.00% increase; and the false negative rates at levels 8 and 9 were reduced by 2.42% and 6.76%, respectively. The system efficacy of the high-density SNP locus set for kinship inference of first to eighth degree relationships reached 98.91%. Through random reduction of the high-density SNP locus set results, it is found that increasing the number of SNPs with the panel, the detection efficiency of IBD length showed a significant upward trend. At the same time, the overall trend in the accuracy of kinship relationship prediction as well as the confidence interval accuracy also indicated that both metrics steadily increased with the addition of more loci. ConclusionThe results show that the high-density SNPs panel significantly enhances the efficacy of distant kinship inference, accurately covering kinship degrees, with the average confidence interval accuracy for first to eighth degree relationships stably above 90%. The study finds that increasing the number of SNPs panel can improve the ability to predict distant kinship.

The study focuses on the concept of multifunctional traditional Chinese medicine (TCM) formulas and aims to evaluate the efficacy of the classical formula Xiaoyao San (逍遥散). Study employs the integrated evidence chain (Eff-iEC) method to organize, integrate, and evaluate its therapeutic efficacy in treating different diseases with the same therapy, and to investigate the feasibility of using Eff-iEC to evaluate the multifunctionality of TCM formulas. The evaluation covered Xiaoyao San's therapeutic effects on depression, premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Concurrently, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for evaluation, and authoritative medical documents were incorporated to corroborate the recognition of Xiaoyao San within the medical community. Depression and menopausal syndrome received higher ratings than other conditions in the Eff-iEC, GRADE, and Medical Community Recognition assessments. The Eff-iEC evidence grade for Xiaoyao San was rated as "High" or above for chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Premenstrual syndrome received a "Moderate ⁺" rating. The GRADE evidence level was "Low-〇〇⨁⨁" for depression, premenstrual syndrome, and chronic hepatitis; "Moderate-〇⨁⨁⨁" for dyspepsia and menopausal syndrome; and "Very Low-〇〇〇⨁" for irritable bowel syndrome. Depression and menopausal syndrome had the highest inclusion frequency, appearing in all 4 categories. Premenstrual syndrome, chronic hepatitis, and dyspepsia are not recommended in Western medical guidelines, but they are included in TCM guidelines, the China National Basic Medical Insurance Drug List, and the China National Essential Drug List. Irritable bowel syndrome appears only in the China National Basic Medical Insurance Drug List and China National Essential Drug List. The evaluation results obtained using the Eff-iEC method align with Medical Community Recognition, providing an objective and comprehensive assessment of Xiaoyao San's efficacy. The findings suggest that Xiaoyao San has strong evidence for treating depression and menopausal syndrome. However, further experimental and clinical trials are needed to assess its efficacy in treating premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, and dyspepsia. These results support the clinical efficacy and rational use of Xiaoyao San, expand the application scope of the Eff-iEC method, and offer valuable insights and methodological references for the comparative evaluation of multifunctional TCM formulas.

Objective To investigate the associations of shear wave elastography (SWE) parameters and AST-to-platelet ratio index (APRI) with Child-Pugh grade in patients with hepatitis B cirrhosis. Methods The clinical data of 103 patients with hepatitis B cirrhosis who underwent SWE and APRI testing between July 2022 and October 2024 were retrospectively analyzed. These patients comprised the observation group. The clinical data of 99 non-cirrhotic patients were retrospectively analyzed and the patients were enrolled as control group. Liver stiffness (LS), spleen stiffness (SS), APRI and Child-Pugh score were compared in the two groups. According to Child-Pugh grading, the 103 cirrhosis patients were divided into three groups: Group A (grade A, 5-6 points, n=35), Group B (grade B, 7-9 points, n=38), and Group C (grade C, 10-15 points, n=30). SWE parameters and APRI were compared among the three groups. Pearson correlation analysis was used to examine the correlations of LS, SS, and APRI with Child-Pugh score. Results SWE parameters, APRI, and Child-Pugh scores were significantly higher in the observation group than in the control group (P<0.05). Among the three cirrhosis groups, SWE parameters and APRI were highest in Group C, followed by Group B, and lowest in Group A (P<0.05). SWE parameters and APRI were significantly positively correlated with Child-Pugh score (P<0.05). Conclusion SWE parameters and APRI are positively correlated with Child-Pugh grade and are useful for assessing the severity of liver cirrhosis.

Objective To establish a chromatography-tandem mass spectrometry method for detecting chlorfenapyr and its metabolite tralopyril in blood,and to investigate the toxicokinetics in rats.Methods Chlorfenapyr(8 mg/kg)was administered orally to rats,and blood samples were collected from rats'canthus vein at 5 min,15 min,30 min,1 h,3 h,6 h,12 h,24 h and 48 h after administration.The blood samples were extracted using 100 μL of 5%formic acid solution and 400 μL of acetonitrile.Chlorfena-pyr was qualitatively and quantitatively detected by triple quadrupole gas chromatography-tandem mass spectrometry(GC-MS/MS)and tralopyril was detected by triple quadrupole liquid chromatography-tandem mass spectrometry(LC-MS/MS).The DAS 3.0 software was used to fit the toxicokinetic equa-tions and calculate the toxicokinetic parameters.Results Chlorfenapyr was detectable from 5 min to 24 h with a peak time of 1 h.Tralopyril was detectable from 15 min to 48 h with a peak time of 3 h.The toxicokinetic process of chlorfenapyr in rat blood conformed to a first-order absorption one-compartment open model,with the toxicokinetic equation described as C=e-0.265t-e-0.175t.Tralopyril con-formed to the first-order absorption three-compartment model,and the toxicokinetic equation was C=47 361.069e-2.209t-35 404.962e-1.486t+11 956.363e-0.512t.In the equations,C stands for the concentration of the target substance in the blood,e is the natural constant(≈2.718 28),and t stands for time.Conclu-sion This study optimized the detection method for chlorfenapyr and its metabolite tralopyril in blood.The toxicokinetic equations and parameters of chlorfenapyr and tralopyril can provide a reference for the estimation of oral intake time of chlorfenapyr.

Objective To investigate the expression and clinical significance of B7-H5 in patients with chro-nic hepatitis B and hepatitis B virus(HBV)-related hepatocellular carcinoma.Methods Enzyme-linked immu-nosorbent assay(ELISA)was used to detect the serum levels of B7-H5 in 104 patients with chronic hepatitis B,28 patients with HBV-related hepatocellular carcinoma and 35 healthy controls.And statistical methods were used to analyze the difference,correlation and diagnostic value of the results.Results The serum levels of B7-H5 in patients with HBV-related hepatocellular carcinoma,patients with chronic hepatitis B and healthy subjects were statistically different(P＜0.05),and the level from high to low was HBV-related liver cancer patients,chronic hepatitis B patients,healthy subjects.The serum level of B7-H5 in chronic hepatitis B pa-tients with negative HBV-DNA was significantly higher than that in healthy subjects(P＜0.01).The level of B7-H5 in patients with chronic hepatitis B was positively correlated with HBV-DNA load(P＜0.05).And the level of B7-H5 in patients with HBV-related hepatocellular carcinoma was positively correlated with HBsAg,HBeAg and AFP levels(P＜0.05).In addition,B7-H5 had diagnostic value for chronic hepatitis B and HBV-related hepatocellular carcinoma(P＜0.01),and the diagnostic value for HBV-related hepatocellular carcino-ma was higher than that for chronic hepatitis B.The level of B7-H5 in patients with HBV-related hepatocellu-lar carcinoma after surgery was significantly lower than that before surgery(P＜0.05).Conclusion Serum levels of B7-H5 is related to the progression of CHB and HBV-related hepatocellular carcinoma,and can be considered as an effective detection index for the auxiliary diagnosis and the judgment of postoperative condi-tion of CHB and HBV-related hepatocellular carcinoma.

Objective:To explore the clinical efficacy of transcranial ultrasound stimulation combined with low-frequency neuromuscular electrical stimulation on the treatment of cognitive and motor function deficits in stroke patients.Methods:Ninety patients with cerebral hemorrhage in the rehabilitation department from July 2023 to July 2024 were selected and divided into control group( n=44)and observation group( n=46)randomly.The control group received conventional rehabilitation methods and low-frequency neuromuscular electrical stimulation rehabilitation treatment, while the observation group received transcranial ultrasound treatment in addition.Mini-mental state examination (MMSE), simplified Fugl-Meyer assessment (SFMA), modified Barthel index (MBI) and Brunnstrom movement therapy phase were used to evaluate the effectiveness of cognitive and motor rehabilitation treatment for all stroke patients.The data were analyzed by paired t-test, independent sample t-test, and Mann-Whitney U test using SPSS 26.0 software. Results:After treatment, the scores of MMSE (observation group: 26.12±2.24, control group: 23.08±1.56), SFMA(observation group: 24.83±9.02, control group: 17.24±9.51), and MBI(observation group: 68.00±7.03, control group: 49.66±7.98) of both groups were significantly higher than those before treatment(MMSE(observation group: 21.32±2.11, control group: 21.56±1.96), SFMA(observation group: 10.43±8.05, control group: 10.56±7.63), MBI (observation group: 32.34±7.65, control group: 32.00±9.73)), and the differences were all statistically significant ( t=-18.13--2.31, all P<0.05).The scores of MMSE, SFMA, and MBI in observation group were all higher than those of the control group, with statistically significant differences( t=-4.45, -4.51, -5.59, all P<0.05). After treatment, the observation group had more patients with Brunstrom stage Ⅳ or above in the affected upper limb ( Z=-6.236, P=0.045) and lower limb ( Z=-6.589, P=0.036) compared to the control group. There were more patients in both two groups with grade Ⅳ or above in the affected lower limb than in the affected upper limb ( P<0.05). Conclusion:The combination of transcranial ultrasound stimulation therapy and low-frequency neuromuscular electrical stimulation therapy can significantly improve cognitive and motor dysfunction in stroke patients. It can be used for the rehabilitation treatment of cognitive and motor dysfunction in stroke patients.

Objective To investigate the brain voxel-mirrored homotopic connectivity(VMHC)alterations in patients with ves-tibular migraine(VM)by using resting-state functional magnetic resonance imaging(rs-fMRI).Methods The rs-fMRI data of 30 VM patients(VM group)and 30 healthy volunteers(control group)were prospectively collected.The brain VMHC values in all subjects were calculated and the differences between the two groups were compared.The correlations between VMHC values of significant brain regions and clinical scale scores were analyzed in the VM group.Results Compared with the control group,the VMHC values of the cerebellum region 6,orbital inferior frontal gyrus,insula,superior temporal gyrus and postcentral gyrus in the VM group were all decreased[cluster-level family wise error(FWE)corrected,Pvoxel-level<0.001,Pcluster-level<0.05].In the VM group,the VMHC values of the postcentral gyrus were negatively correlated with dizziness handicap inventory(DHI)score(r=-0.383,P=0.037).Additionally,the VMHC values of the insula were negatively correlated with headache impact test-6(HIT-6)score(r=-0.430,P=0.018).Conclusion VM patients have altered VMHC in certain brain regions,indicating related dysfunctions in vestibule,pain,hearing and emotion.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.