ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

Objective To observe value of real-time functional MRI neurofeedback(rtfMRI-NF)for modulating brain activity changes in obese adults.Methods Twenty-two obese adults were prospectively recruited,3-week rtfMRI-NF training intervention was conducted.Barratt impulsivityness scale version 11(BIS-11),three-factor eating questionnaire(TFEQ)and food rating scales were scored before and after intervention,and whole-brain resting state fMRI(rs-fMRI)data were obtained.Clinical scale scores,rs-fMRI regional homogeneity(ReHo)values and amplitude of low frequency fluctuation(ALFF)values were compared before and after intervention.Then brain regions with differences of ReHo and ALFF values before and after intervention were explored,and correlations of values of rs-fMRI data differences and clinical scale score differences were analyzed.Results BIS-11 score,TFEQ emotional eating(TFEQ-EE)score and food rating scales scores decreased,while TFEQ cognitive restraint(TFEQ-CR)scores increased in obese adults after intervention(all P＜0.05).ReHo values in right inferior frontal gyrus,right anterior cingulate and left precuneus increased,while of left middle temporal gyrus decreased(all corrected P＜0.05).ALFF values of left precuneus increased,whereas of left middle occipital gyrus,right superior occipital gyrus,left calcarine fissure and surrounding cortex and left supramarginal and angular gyrus decreased(all corrected P＜0.05).ReHo difference in right anterior cingulate was negatively correlated with BIS-11 scores difference(r=-0.601,P＜0.05),and ALFF difference in left precuneus was negatively correlated with TFEQ-EE difference(r=-0.478,P＜0.05).Conclusion rtfMRI-NF intervention could correct disorder of cerebral functional areas in obese adults and change high-calorie food preference and poor dietary habits.

Objective To investigate the relationship between platelet distribution width(PDW)and coronary artery calcification(CAC)in overweight and obese populations.Methods Clinical and chest CT data of 10 838 subjects with overweight or obesity(body mass index[BMI]≥24 kg/m2)were retrospectively analyzed.The subjects were divided into CAC group(n=4 237)and non-CAC group(n=6 601)based on CAC scores obtained from chest CT.The relationship between PDW and CAC in overweight and obese populations was analyzed after controlling confounding variables.A threshold effect analysis was conducted using a two-stage logistic model to find the non-linear inflection point.Subgroup analyses and interaction tests were conducted to validate the stability of the relationship between PDW and CAC.Results Non-linear relationship was observed between PDW and CAC risk in overweight and obese populations.The risk of CAC decreased with the increase of PDW which ≤17.80％(OR=0.82),but increased with the increase of PDW(OR=1.04)which＞17.80％.Subgroup analysis showed that the relationship between PDW and CAC remained stable in subgroups of different genders,BMI(＜28 kg/m2,≥28 kg/m2)and hypertension(all P＞0.05).Compared with aged＜40 years or ≥60 years subgroups,under the same PDW,aged≥40 and＜60 years subgroups had higher risk of CAC(interaction P=0.015).Conclusion Nonlinear relationship existed between PDW and CAC in overweight and obese populations.Both excessively high and low PDW were risk factors of CAC.

This article reviews the benifits and challenges of nano-microspheres (NPs) in the treatment of osteoarthritis (OA). OA is a degenerative disease associated with aging, trauma, and excessive loading, with treatment strategies including basic therapy, drug therapy, reparative therapy, and reconstructive surgery. As emerging nanomaterials, NPs offer unique advantages in promoting cartilage repair due to their high surface area, excellent drug-loading capacity, and good biocompatibility. These advantages include facilitating chondrocyte generation through magnetic-mechanical control of mesenchymal stem cell microspheres and enhancing antioxidant levels using biomimetic liposomal NPs combined with glucosamine. Additionally, NPs can effectively modulate inflammatory responses, such as by inhibiting the formation of M1 macrophages and promoting their polarization to the M2 type to alleviate inflammation. Some NPs also enhance joint lubrication and relieve pain, such as hyaluronic acid-based NPs modified with choline phosphate groups. However, the application of NPs faces challenges such as high production costs, poor biocompatibility for certain types, and unknown long-term safety. Despite these challenges, with advancements in nanotechnology and a deeper understanding of the pathological mechanisms of OA, NPs are expected to provide new therapeutic approaches and more comprehensive and effective treatment options for OA patients in the future.

Objective:To analyze the prevalence and clinical characteristics of pertussis in children with different cough durations.Methods:From January 2021 to October 2022, information on children aged 0-18 years who visited eight hospitals in Shandong Province due to cough was enrolled. Pertussis serological antibody testing and/or nucleic acid testing were performed. The prevalence and clinical characteristics of pertussis were compared among the acute cough group, protracted cough group, and chronic cough group using the χ2 test or Fisher′s exact test. Results:A total of 1 565 children with cough were included in the study, of which 348 (22.24%) were laboratory-confirmed pertussis. There was a significant difference in the laboratory-confirmed rate of pertussis among different cough groups ( χ2=83.424, P<0.001). The confirmation rate of pertussis in the protracted cough group (42.21%) was significantly higher than that in the acute cough group (16.49%, P<0.05) and chronic cough group (19.50%, P<0.05). In each cough group, the age of children was significantly associated with the confirmed rate of pertussis, and the confirmed rate was relatively high in children aged 3 months to <2 years. Pertussis vaccination was significantly associated with the confirmed rate in all groups, and the confirmed rate was higher in unvaccinated children. Among laboratory-confirmed pertussis cases, the incidence of typical symptoms such as paroxysmal cough, whoop, and post-tussive emesis or sleep disturbance was significantly higher than that in the non-confirmed cases. In the protracted and chronic cough groups, the proportion of non-confirmed cases complicated with asthma/cough variant asthma (CVA) was significantly higher than that in pertussis-confirmed cases. Conclusion:There are differences in the confirmation rate of pertussis among children with different cough durations. The confirmation rate is significantly associated with age, vaccination status, and clinical symptoms. Enhancing clinical vigilance against pertussis, conducting early diagnosis, and getting timely and standardized vaccination are crucial for effectively controlling pertussis and preventing outbreaks.

Objective:To analyze the multidrug resistance and genomic characteristics of Monophasic variant of Salmonella enterica serovar Typhimurium (monophasic Salmonella enterica serovar Typhimurium) isolates from clinical patients and food sources in Henan province. Method:A total of 91 monophasic S.Typhimurium strains isolated from clinical and food sources in Henan from 2021 to 2023 were analyzed for antimicrobial sensitivity and underwent whole genome sequencing. Multilocus sequence typing(MLST), multidrug resistance genes and plasmid types were identified using the sequencing data. Phylogenetic tree based on core genome multilocus sequence typing (cgMLST) and single nucleotide polymorphism (SNP) sites was constructed to analyze the genetic evolutionary relationship by comparing with international popular strains in public databases. The Chi-square test was used to compare drug resistance rates. Results:No significant difference was observed in the drug resistance rates between the clinical strains and food strains in Henan [82.19%(60/73) and 11/18, χ2=2.614, P=0.106]. The overall multidrug resistance (MDR) rate was 78.02%(71/91). Most strains were resistant to ampicillin, tetracycline chloramphenicol, β-lactam and sulfonamides. Resistance genes carried by the isolates varied, as well as the drug-resistant phenotypes. MLST showed that 91 strains of S.Typhimurium belonged to ST34 and carried aminoglycoside acetyltransferase gene aac(6′)-Iaa and mobile genetic elements such as plasmids IncQ1 and IncHI2/IncHI2A. The results of cgMLST typing phylogenetic trees showed that food and clinical isolates from the same region in Henan were identified as the same cgST type and clustered in the same branch, which indicated the risk for cross-infection between animal and human. The phylogenetic tree of monophasic S.Typhimurium constructed based on SNP sites showed that the majority of monophasic S.Typhimurium strains in Henan were close to the strains from other provinces in China, other strains were close to the strains from Europe and Southeast Asia, suggesting the possibility of cross regional transmission of the strains. Pork was identified as the main food source. Conclusion:The prevalent ST type of monophasic S.Typhimurium isolated from Henan was ST34, which carried multiple antibiotic resistance genes and widespread drug resistance phenotypes. Most of the monophasic S.Typhimurium isolates in Henan showed a specific phylogenetic lineage with the foreign epidemic strains, indicating the possibility of dissemination of strains between humans and food.

Objective:To explore the correlation between the lesion imaging characteristics and the parent artery plaques detected by high-resolution magnetic resonance imaging (HR-MRI) in patients with recent small subcortical infarction (RSSI) in the lenticulostriate artery territory with mild stenosis of the parent artery.Methods:Consecutive patients with RSSI in the lenticulostriate artery territory admitted to Department of Neurology, the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were prospectively enrolled. Patients with stenosis of <50% in the ipsilateral middle cerebral artery (MCA) who had completed HR-MRI were included. The RSSI lesion characteristics, such as the lowest slice involved (LS), total number of slices involved (TNS) were evaluated based on serialized axial levels of diffusion weighted imaging. HR-MRI was utilized to assess the presence of dorsal superior plaques in the M1 segment of the responsible MCA. Patients were divided into plaque group and non-plaque group based on the presence or absence of plaque. Logistic regression analysis was carried out to identify the lesion characteristics associated with the presence of dorsal superior plaques in the MCA. A receiver operating characteristic (ROC) curve was employed to estimate the predictive efficacy of these parameters for MCA plaques using the area under the curve (AUC) and the optimal cut-off point.Results:A total of 112 patients were incorporated into the final analysis. The age of these patients was (57.08±11.90) years, and 78 patients (69.64%) were male. Plaques were detected on the dorsal superior wall of the MCA in 57 cases (50.89%) as the plaque group, and the other 55 cases (49.11%) were regarded as the non-plaque group. Multivariate Logistic regression revealed that LS was significantly associated with MCA plaques ( OR=0.674, 95% CI 0.485-0.937, P=0.019). The optimal cut-off point (LS≤1) was determined by ROC curve analysis (AUC=0.640, P=0.007). Conclusion:The findings suggest that in RSSI patients with mild stenosis of the parent artery, an LS≤1 is notably associated with the presence of dorsal superior plaques on MCA as detected by HR-MRI.

BACKGROUND:It has been found that mitochondrial function is abnormal in patients with chronic fatigue syndrome,and the administration of coenzymes can improve the symptoms.Warm acupuncture is one of the most important treatments for this disease,but its mechanism of action is unclear. OBJECTIVE:To investigate the effects of warm acupuncture on the phosphatase and tensin inducible kinase 1(PINK1)/Parkin pathway in the skeletal muscle of rats with chronic fatigue syndrome. METHODS:After 3 days of adaptive feeding,32 male Sprague-Dawley rats were randomly divided into normal control,model,warm acupuncture,and coenzyme Q groups with 8 rats in each group.The chronic fatigue syndrome model was established by multiple factors,including swimming exhaustion,chronic immobilization and fasting.After successful modeling,the normal group and the model group were treated with the same fixation and gavage procedures,and the warm acupuncture group was treated with acupuncture at Guanyuan,Zhongwan and Zusanli(bilateral)points,once a day.After the needling was inserted,the moxa pillar was put on the needle handle and ignited,three sessions once.The coenzyme Q group was given 1 mL/kg coenzyme by gavage,once a day for 14 days.The body mass,exhaustive swimming time and food utilization rate during the treatment were recorded.After the treatment,the bilateral gastrocnemius muscles of rats in each group were collected.The pathological morphology of the gastrocnemius muscle was observed by hematoxylin-eosin staining,the mitochondrial morphology and autophagosome of the gastrocnemius muscle were observed by transmission electron microscope.The expression level of microtubule-associated protein light chain 3(LC3)Ⅱ protein in the skeletal muscle was detected by immunohistochemistry.Western blot was used to detect the expression of PINK1,Parkin,LC3 Ⅰ,and LC3 Ⅱ in the skeletal muscle. RESULTS AND CONCLUSION:Compared with the normal group,the gastrocnemius muscle nuclei of the model group were pyknotic,condensed,the number of cells was increased,the cells were arranged disorderly,and the fibers in the gastrocnemius muscle were tightly arranged in the model group.Compared with the model group,the intercellular space became smaller,the nuclei were reduced,and the cell arrangement was orderly in the warm acupuncture group and coenzyme Q group.Compared with the normal group,the skeletal muscle mitochondria in the model group were swollen,fused,and vacuolated seriously,the membrane was partially broken,the matrix was more dissolved,the cristae was broken and disappeared,and autophagy appeared.Compared with the model group,the number of mitochondria increased,the arrangement was relatively neat,mitochondrial vacuolization and rupture of cristae in the gastrocnemius muscle were improved,the membrane structure was relatively intact,and autophagy occurred.Compared with the normal group,the expression of PINK1 protein in the skeletal muscle of the model group was significantly increased(P<0.05),while the expression of Parkin,LC3 Ⅱ and LC3 Ⅱ/Ⅰ protein was slightly upregulated(P>0.05).Compared with the model group,the protein expressions of PINK1,Parkin,LC3 Ⅱ and LC3 Ⅱ/Ⅰ were significantly upregulated in the warm acupuncture and coenzyme Q groups(P<0.05),and the up-regulation was more significant in the warm acupuncture group.To conclude,warm acupuncture can play a role in the treatment of chronic fatigue syndrome by activating the PINK1/Parkin pathway,upregulating LC3 Ⅱ expression,forming mitochondrial autophagosomes,promoting the degradation of damaged mitochondria,and improving mitochondrial quality.

Objective To comprehensively understand the map of transcripts during mitosis and their regulatory mechanisms of HAP 1 cells by conducting transcriptome sequencing analysis after being released by mitotic synchro-nization arrest.Methods HAP1 cells were subjected to mitotic synchronous arrest with nocodazole and samples were collected after 0,20,80 min release,and RNA sequencing(RNA-seq)were performed.The transcriptome data was cleaned and the differentially expressed genes,expression trend clustering and functional enrichment com-bined with the protein interaction network were analyzed to explore the changes of signaling pathways in HAP 1 cells during mitosis.Results The transcriptome of HAP1 cells after synchronous release from mitosis underwent significant changes in time series,and differential gene cluster analysis revealed four gene clusters were enriched in important biological processes such as p53 signaling and cytoplasmic translation.Conclusions The transcriptome time-dependent dynamic changes during mitosis in HAP1 cells are coordinated regulation of key signaling pathways including cellular stress response,translational control and chromatin remodeling,ensuring a balance between growth and stress response upon mitotic exit.

Objective To explore the effects of 1 800 MHz electromagnetic radiation(EMR)on cognitive function of 3xTg-AD and 57C mice,providing a theoretical basis for the potential impacts of electromagnetic radiation on the human body.Methods A total of 12 3xTg-AD transgenic mice and 12 wild-type C57 mice were selected as research subjects.The one-month-old mice were divided into four groups:RF WT,Control WT,RF AD,and Control AD,with 6 mice in each group.The 1 800 MHz EMR exposure experiments were conducted from 20:00 to 8:00 the next day for a duration of 5 months.After the exposure,a water maze test was conducted to evaluate the effects of EMR on spatial learning and memory abilities of 3xTg AD mice,along with measurements of body weight,brain weight,and calculation of the brain-to-body ratio.Finally,Western Blot technique was used to measure the levels of APP,NR1,and NR2A in hippocampal tissue to analyze effects of 1 800 MHz EMR on the cognitive function of 3xTg AD mice.Results Under 1 800 MHz EMR exposure,there were no statistically significant differences in Morris water maze spatial learning ability among the four groups(P>0.05).However,longer escape time,greater swimming distances,and more crossings of target quadrant were exhibited in the RF AD group compared to the other groups(P<0.05).Western Blot results showed that the APP protein levels in 3xTg AD mice was higher than those in C57 mice(P<0.05).The expression levels of NR1 protein in the WT group was higher than those in the AD group(P<0.05);in the AD group,the RF AD group had higher levels than the Control WT group(P<0.05),and the NR2A protein levels in the Control WT group were higher than in the other groups(P<0.05).Conclusion Prolonged exposure to 1 800 MHz EMR can affect the learning and cognitive function of both 3xTg AD and C57 mice.