Objective To investigate the characteristics of macrophage depletion by clodronate liposomes(CL)in a carbon tetrachloride(CCl4)-induced liver fibrosis mouse model,and to analyze the transcriptomic features.Methods Thirty-two C57BL/6 mice were divided randomly into plain control liposomes for clophosome(PL)and clodronate liposome(CL)groups(n=16 mice per group),and administered intraperitoneal injections of PL and CL,respectively.On day 5,each group was further divided into normal(N)and model(M)subgroups(n=8 mice per subgroup).Mice in group M received 10％CCl4 intraperitoneally to induce liver fibrosis,while mice in group N received an equal volume of olive oil.After 4 weeks,serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were measured,and hepatic inflammation and collagen deposition were evaluated by hematoxylin/eosin and Sirius red staining,respectively.Total RNA was extracted from liver tissues for transcriptomic sequencing and subsequent differential gene expression analysis.Results Serum ALT and AST levels were significantly elevated in the PL-M group(P＜0.01),with fibrosis staging primarily at S3,compared with S1 in the CL-M group.Totals of 1462 and 2119 differentially expressed genes(|log fold change|＞2 and P＜0.05)were identified in the PL and CL groups,respectively.Gene Ontology analysis revealed enrichment in multiple biological processes,cellular components,and molecular functions in both models,and Kyoto Encyclopedia of Genes and Genomes analysis identified 29 significantly enriched pathways(P＜0.05).The upregulation of genes including Lgals7 and Timp1 and the downregulation of Mup-ps16 and Mup15 were validated by reverse transcription-quantitative polymerase chain reaction,consistent with transcriptomic trends(P＜0.05).Conclusions This study highlights the characteristics and transcriptomic features of macrophage depletion in the CCl4-induced liver fibrosis model,providing a theoretical reference for research on the immune mechanisms of liver fibrosis.

Objective To analyze the epidemiological characteristics of human papillomavirus(HPV)infection in women in the Zhongguancun area of Beijing,and to evaluate the infection rates and genotype distribution between different populations and age groups.Methods A retrospective analysis was conducted on HPV genotyping results of 13,105 women who visited the gynecology outpatient department or underwent routine health check-ups at Zhongguancun Hospital from March 2019 to April 2024.High-risk HPV genotypes(15 types)were detected using a fluorescence PCR assay.Positive cases were classified as single,dual or multiple(≥3)infections based on the number of genotypes.Subjects were stratified into six age groups(≤30,31-40,41-50,51-60,61-70,and≥71 years),and the characteristics of infection by type and age group were analyzed.Results The overall HPV positivity rate was 10.78%(1,413/13,105),with a significantly higher rate in the outpatient group than that in the health check-up group(16.36%vs.6.06%,P<0.01).The three most prevalent genotypes were HPV52(18.83%),HPV58(13.85%),and HPV16(11.28%).Single infections accounted for 79.19%of cases,dual infections for 15.93%and multiple infections for 4.88%.Age distribution showed a U-shaped pattern,with higher infection rate in women aged≤30 years(15.06%)and 61-70 years(13.19%),and the lowest rate in the≥71 years(8.09%).Notably,women aged≤30 years had the highest proportion of multiple infections(31.72%).Conclusion These findings provide a basis for cervical cancer screening strategies,HPV vaccination promotion and individualized prevention of cervical cancer in this region.

Objective:To construct a continuity of care plan for adolescent fixed orthodontic patients based on the theory of timing, and provide systematic and standardized nursing interventions for adolescent fixed orthodontic patients.Methods:Guided by the theory of timing, preliminary plan items were formulated through literature review and questionnaire survey. Using the Delphi method, 15 experts were consulted for two rounds to determine the continuity of care plan for adolescent fixed orthodontic patients from October to December, 2023.Results:The effective response rates of the two rounds of questionnaires were 15/15, respectively. The expert authority levels were 0.93 and 0.94, and the Kendall harmony coefficients were 0.28 and 0.38, respectively. The differences were statistically significant (both P<0.001). The final established plan included 5 primary indicators, 23 secondary indicators, and 47 tertiary indicators. Conclusions:The continuity of care plan for adolescent fixed orthodontic patients based on the timing theory is reliable and scientific, and can meet the continuity of care needs of patients at different stages, providing reliable clinical basis for carrying out continuity of care.

Objective:To analyze postictal electroencephalographic(EEG) characteristics of patients with status epilepticus (SE) based on the score of grand total electroencephalography (GTE), and explore the relationship between electroencephalographic characteristics of SE and clinical prognosis.Methods:A total of 110 SE patients were enrolled in the Department of Neurology, the Affiliated Hospital of Yangzhou University from September 1, 2021 to September 1, 2023. EEG and GTE scores were performed in all patients after seizures (0-2 days after the cessation of SE). After one year of discharge, the medication and seizure status of patients were followed up by phone or outpatient visits. The seizure outcomes were recorded according to the international league against epilepsy (ILAE) seizure outcome classification, with favorable outcomes defined as good prognosis group ( n=54) and unfavorable outcomes defined as poor prognosis group ( n=56). SPSS 27.0 software was used for statistical analysis. Binary Logistic regression analysis was employed to screen impact variables of prognosis. The receiver operating characteristic(ROC) curve was plotted to determine the optimal cut-off point for predicting prognosis in epilepsy. Results:There were statistically significant differences in the total GTE score(2(1, 4), 8(5, 10); Z=-6.837, P<0.001), diffuse slow activity(0(0, 1), 2(0, 2); Z=-6.495, P<0.001), reactivity of the rhythmic background activity(0(0, 0), 0(0, 1); Z=-2.705, P=0.007), paroxysmal activity(0(0, 0), 1.5(0, 3.0); Z=-4.420, P<0.001), focal disturbances(0(0, 0), 0(0, 0); Z=-2.130, P=0.033), and sharp wave activity(0(0, 2), 2(2, 3); Z=-5.714, P<0.001)between the good prognosis group and poor prognosis group. The differences in EEG results among SE patients with different types of epileptic seizures were statistically significant in terms of frequency of rhythmic background activity, diffuse slow activity, reactivity of rhythmic background activity and total GTE score (all P<0.05). The differences in EEG results between SE patients with clear and unknown causes were statistically significant in terms of paroxysmal activity and focal disturbances(both P<0.05). The results of binary Logistic regression analysis showed that independent factors associated with the prognosis of SE included medication adherence ( B=-0.496, OR=0.609, 95% CI=0.395-0.940, P=0.025), diffuse slow activity( B=1.580, OR=4.854, 95% CI=1.586-14.855, P=0.006), sharp wave activity( B=0.824, OR=2.280, 95% CI=1.210-4.297, P=0.011), and total GTE score ( B=0.561, OR=1.753, 95% CI=1.360-2.259, P<0.001). In evaluating the prognosis of SE, the GTE score had a certain sensitivity (74.6%) and specificity (85.1%), with a optimal cut-off point of 6. Conclusions:The differences in EEG results among SE patients with different types of epileptic seizures were statistically significant in terms of frequency of rhythmic background activity, diffuse slow activity, reactivity of rhythmic background activity. The appearance of diffuse slow activity and sharp wave activity in the electroencephalogram of SE patients indicates poor prognosis, and the total GTE score≥6 may be a strong predictor of poor prognosis. However, good medication adherence is a protective factor for epilepsy recurrence.

Objective:To analyze postictal electroencephalographic(EEG) characteristics of patients with status epilepticus (SE) based on the score of grand total electroencephalography (GTE), and explore the relationship between electroencephalographic characteristics of SE and clinical prognosis.Methods:A total of 110 SE patients were enrolled in the Department of Neurology, the Affiliated Hospital of Yangzhou University from September 1, 2021 to September 1, 2023. EEG and GTE scores were performed in all patients after seizures (0-2 days after the cessation of SE). After one year of discharge, the medication and seizure status of patients were followed up by phone or outpatient visits. The seizure outcomes were recorded according to the international league against epilepsy (ILAE) seizure outcome classification, with favorable outcomes defined as good prognosis group ( n=54) and unfavorable outcomes defined as poor prognosis group ( n=56). SPSS 27.0 software was used for statistical analysis. Binary Logistic regression analysis was employed to screen impact variables of prognosis. The receiver operating characteristic(ROC) curve was plotted to determine the optimal cut-off point for predicting prognosis in epilepsy. Results:There were statistically significant differences in the total GTE score(2(1, 4), 8(5, 10); Z=-6.837, P<0.001), diffuse slow activity(0(0, 1), 2(0, 2); Z=-6.495, P<0.001), reactivity of the rhythmic background activity(0(0, 0), 0(0, 1); Z=-2.705, P=0.007), paroxysmal activity(0(0, 0), 1.5(0, 3.0); Z=-4.420, P<0.001), focal disturbances(0(0, 0), 0(0, 0); Z=-2.130, P=0.033), and sharp wave activity(0(0, 2), 2(2, 3); Z=-5.714, P<0.001)between the good prognosis group and poor prognosis group. The differences in EEG results among SE patients with different types of epileptic seizures were statistically significant in terms of frequency of rhythmic background activity, diffuse slow activity, reactivity of rhythmic background activity and total GTE score (all P<0.05). The differences in EEG results between SE patients with clear and unknown causes were statistically significant in terms of paroxysmal activity and focal disturbances(both P<0.05). The results of binary Logistic regression analysis showed that independent factors associated with the prognosis of SE included medication adherence ( B=-0.496, OR=0.609, 95% CI=0.395-0.940, P=0.025), diffuse slow activity( B=1.580, OR=4.854, 95% CI=1.586-14.855, P=0.006), sharp wave activity( B=0.824, OR=2.280, 95% CI=1.210-4.297, P=0.011), and total GTE score ( B=0.561, OR=1.753, 95% CI=1.360-2.259, P<0.001). In evaluating the prognosis of SE, the GTE score had a certain sensitivity (74.6%) and specificity (85.1%), with a optimal cut-off point of 6. Conclusions:The differences in EEG results among SE patients with different types of epileptic seizures were statistically significant in terms of frequency of rhythmic background activity, diffuse slow activity, reactivity of rhythmic background activity. The appearance of diffuse slow activity and sharp wave activity in the electroencephalogram of SE patients indicates poor prognosis, and the total GTE score≥6 may be a strong predictor of poor prognosis. However, good medication adherence is a protective factor for epilepsy recurrence.

Objective To compare the serological and pathological characteristics of 3 nonalcoholic steatohepatitis(NASH)models:high-fat diet(HFD)with carbon tetrachloride(CCl4)injection,methionine and choline deficient diet(MCD),and Aymlin liver NASH(AMLN)diet-induced NASH models.Methods 3 NASH models were established by feeding mice an HFD with CCl4 injection for 10 weeks,MCD for 8 weeks and NASH for 26 weeks.After feeding,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),glucose(GLU),liver triglyceride(TG),total cholesterol(TC),and malondialdehyde(MDA)levels and superoxide dismutase(SOD)activity were measured.Insulin levels were measured by enzyme-linked immunosorbent assay(ELISA)and the homeostasis model assessment of insulin resistant(HOMA-IR)index was calculated.Hematoxylin-eosin(HE),Sirius red,and oil red staining were used to indicate pathological changes to the liver.The NAS score was used to grade the pathology.Results Compared to each normal control(NC)group mice,all mice in the 3 model groups had an obvious increase in serum transaminase and liver TG,TC,MDA levels and SOD activity.The levels of serum FINS,GLU and the HOMA-IR index were significantly increased in the AMLN and CCl4+HFD model groups but decreased in the MCD model group.According to the HE,oil red staining and NAS score,mice in all 3 groups had NASH phenotypic changes.Liver collagen deposition was most obvious in mice in theCCl4+HFD model group.Liver lipid droplets were most abundant in the AMLN model group.Conclusions All the above 3 animal models can stably simulate the serological and pathological changes of NASH in human.The AMLN model can simulate the progress and mechanism of the disease,as well as systemic metabolic disorders such as insulin resistance and oxidative stress.However,it is time-consuming and the fibrosis progression rate is slow.The MCD diet can simulate the serological and pathological features of NASH in 8 weeks,but no obesity or insulin resistance occurred.The CCl4 combined with HFD model can induce NASH model in 10 weeks,which can simulate its serological and pathological changes,and the liver has obvious fibrous deposition and oxidative stress damage.

Objective To explore the correlation between the expression of serum human leukocyte antigen B27(HLA-B27) and serum amyloid A(SAA) in patients with pulmonary tuberculosis and the severity of the disease and the infection of other pulmonary pathogens. Methods From September 2021 to September 2023,120 patients with pulmonary tuberculosis complicated with pulmonary infection in Beijing Ditan Hospital Affiliated to Capital Medical University were selected as the research group,and another 120 patients with pulmonary tuberculosis were selected as the control group. According to the pneumonia severity index (PSI),the study group patients were divided into low-risk group (n=47),medium risk group (n=42) and high-risk group (n=31). Collected patient sputum for pathogen detection. Enzyme-linked immunosorbent assay (ELISA) was applied to measure the expression levels of HLA-B27 and SAA in serum. Multivariate Logistic regression was applied to analyze the factors that affected the severity of pulmonary tuberculosis combined with pulmonary infection in patients. Receiver operating characteristic (ROC) curve was applied to analyze the diagnostic efficacy of serum HLA-B27 and SAA for the severity of pulmonary tuberculosis combined with pulmonary infection in patients. Results Compared with the control group,the positive rate of serum HLA-B27(72.50％ vs 19.17％)in the study group,expression level of SAA (9.32±2.32 ng/ml vs 4.64±1.04 ng/ml)were significantly increased,and the differences were statistically significant(x2=68.744,t=20.164,all P<0.05). A total of 84 strains of pathogenic bacteria were isolated by the research group,including 46 Gram negative bacteria,34 Gram positive bacteria,and 4 fungi,with Klebsiella pneumoniae accounting for the highest proportion (15.48％). Compared with the low-risk group,the positive rate of HLA-B27(76.19％,93.55％ vs 55.32％),the expression level of SAA(9.35±2.35ng/ml,10.94±2.42ng/ml vs 8.23±2.23ng/ml)and the PSI score(108.63±12.47score,145.93±12.44 score vs 54.48±17.31 score) in the middle-risk group and the severe-risk group were significantly higher,and the differences were statistically significant (x2=4.256,13.130,t=2.306,5.077;15.021,25.384,all P<0.05). Serum HLA-B27 and SAA levels in patients with pulmonary tuberculosis complicated with pulmonary infection were positively correlated with PSI score (r=0.385,0.522,all P<0.05). The results of multivariate Logistic regression analysis showed that HLA-B27 positivity and SAA were risk factors affecting the severity of pulmonary tuberculosis combined with pulmonary infection in patients (P<0.05). The combined diagnosis of serum HLA-B27 and SAA had the highest area under the curve (AUC) for the severity of pulmonary infection in patients,which was superior to the individual diagnosis of serum HLA-B27 and elevated SAA expression levels (Z=3.132,2.131,P=0.002,0.033). Conclusion The pathogenic bacteria in patients with pulmonary tuberculosis and pulmonary infection are mainly Gram negative bacteria. The increases in serum HLA-B27 positive rate and SAA expression level are closely related to the disease progression in patients with pulmonary tuberculosis and pulmonary infection. The combination of the two can better diagnose the severity of the disease in patients with pulmonary infection.

OBJECTIVES: This study aims to investigate the optimal dose ratio and mechanisms of the primary active components in Yinchenhao decoction (geniposide, chlorogenic acid, and rhubarb polysaccharides) for ameliorating metabolic-associated steatotic liver disease (MASLD). METHODS: C57BL/6 mice were randomly divided into the normal control group, model control group, uniform design groups 1-6, and Yinchenhao Decoction group; except for the normal control group, mice in all other groups were fed a Western diet to establish a MASLD model, and after 8 weeks of modeling, mice in the uniform design groups 1-6 and Yinchenhao Decoction group were given the corresponding drugs by gavage. At 12 weeks, all mice were sacrificed: their body weight and liver weight were measured, hematoxylin-eosin staining was used to observe the histopathological changes of liver tissue, the plasma levels of alanine transaminase (ALT) and aspartate transaminase (AST) were detected, and the levels of total cholesterol (TC) and triglycerides (TG) in plasma and liver were measured. Based on these results, the optimal uniform design group was identified; subsequently, with plasma AST, plasma TG, and liver TC levels as screening indicators, the optimal dose ratio was obtained via a regression equation, which was further verified from two dimensions, namely functional indicators and tissue morphology. Meanwhile, glucose tolerance test and insulin tolerance test were conducted to evaluate glucose metabolic homeostasis and insulin sensitivity in mice, periodic acid-Schiff staining was used to observe glycogen accumulation, quantitative reverse transcription-polymerase chain reaction was employed to detect the mRNA expression of genes related to glycolipid metabolism and bile acid metabolism, Western blotting was performed to measure the protein expression of molecules involved in bile acid metabolism, and commercial kits were used to determine the plasma levels of total bilirubin (TBIL), direct bilirubin (DBIL), and total bile acid (TBA). RESULTS: Combinations of geniposide, chlorogenic acid, and rhubarb polysaccharide all reduced the liver-to-body weight ratio, alleviated liver injury, and decreased lipid accumulation, among which the uniform design group 6 (200 mg/kg geniposide+160 mg/kg chlorogenic acid+340 mg/kg rhubarb polysaccharide) exhibited the optimal efficacy. Meanwhile, regression analysis indicated that the dosage ratio of uniform design group 6 was the optimal one for MASLD intervention. Validation experiments showed that, compared with single-drug intervention, the optimal dosage ratio resulted in significantly lower body weight, as well as lower plasma levels of ALT, AST and TC in mice (all P<0.05), along with a more pronounced reduction in the area of hepatic lipid accumulation. Mechanistic investigation experiments demonstrated that intervention with the optimal dosage ratio significantly improved glucose tolerance and insulin sensitivity in mice (all P<0.05), reduced hepatic glycogen deposition, and downregulated the mRNA expression of glycolipid metabolism-related genes such as Gsk3, G6pc, Pck1, Fbp1, Fasn, Srebp-1c, Scd1, Slc27a2, and Slc27a5 (all P<0.05); it also decreased plasma levels of TBIL, DBIL, and TBA (all P<0.05), reversed the abnormal protein expression of bile salt export pump (BSEP), farnesoid X receptor (FXR), and cholesterol-7α-hydroxylase (CYP7A1) in the liver (all P<0.05), and reversed the abnormal mRNA expression of bile acid metabolism-related genes including Nr1h4, Cyp7a1, Cyp27a1, Slc10a1, and Slco1a1 (all P<0.05). CONCLUSIONS The combination of geniposide (200 mg/kg), chlorogenic acid (160 mg/kg), and rhubarb polysaccharide (340 mg/kg) exerts the optimal ameliorative effect on MASLD in mice. This superior efficacy is presumably achieved by synergistically regulating the key nodes of glycolipid metabolism and bile acid metabolism, ultimately optimizing the therapeutic outcome.

BACKGROUND:Liuwei Dihuang Wan takes"three tonifying and three reducing effects"as its compatibility feature to nourish yin and tonify the kidneys,while Zuogui Wan takes"seeking yin in yang"as its compatibility feature to nourish yin and tonify the kidneys by promoting yang.Both of them belong to the same method of nourishing yin and tonifying the kidneys,and have better curative effects at the symptomatic and cellular molecular levels. OBJECTIVE:To observe the effects of Liuwei Dihuang Wan and Zuogui Wan in bone metabolism,and to explore their mechanism of action in the osteoprotegerin(OPG)/receptor activator of nuclear factor-κB ligand(RANKL)osteoblastic pathway. METHODS:Thirty-two Sprague-Dawley rats were randomized into model,Liuwei Dihuang Wan,Zuogui Wan,and sham operation group,with eight rats in each group.Osteoporosis models were prepared using removal of both ovaries in the first three groups.Starting at 30 days postoperatively,rats in the Liuwei Dihuang Wan group were gavaged with Liuwei Dihuang Wan 1.125 g/kg/d;rats in the Zuoqui Wan group were gavaged with Zuogui Wan 2.25 g/kg/d;and rats in the sham operation group and the model group were gavaged with saline 10 mL/kg/d.After 12 weeks of gavage,the rat tibia was taken to measure bone mineral density.The serum levels of estrogen,bone alkaline phosphatase,and cAMP/cGMP were measured using ELISA,and the expression of OPG/RANKL in the femur was detected using western blot. RESULTS AND CONCLUSION:Compared with the sham operation group,the model group showed a decrease in bone mineral density and levels of estrogen and bone alkaline phosphatase(P＜0.05)and an increase in cAMP/cGMP level(P＜0.05).Compared with the model group,the Liuwei Dihuang Wan group and the Zuogui Wan group significantly increased bone mineral density(P＜0.05)and bone alkaline phosphatase levels(P＜0.05);the Zuogui Wan group significantly decreased cAMP/cGMP levels(P＜0.05)and upregulated OPG expression(P＜0.05);the Liuwei Dihuang Wan group upregulated OPG expression and downregulated RANKL expression(P＜0.05);and both groups were unable to significantly increase estrogen levels(P＞0.05).To conclude,Zuogui Wan,which seeks yin from yang,can effectively increase the expression of OPG but cannot downregulate the expression of RANKL.However,Liuwei Dihuang Wan,which has three tonifying and three reducing effects,can bidirectionally regulate the expression of OPG and RANKL.This result suggests that Liuwei Dihuang Wan can significantly inhibit osteoclastic function compared with Zuogui Wan,and further research is needed to verify this conclusion.

BackgroundAtypical antipsychotics have been widely used in patients with chronic schizophrenia， and aripiprazole and risperidone are the most commonly used drugs. The mechanism of action of the two is different， while previous studies have provided insufficient credible evidence from multiple perspectives to support the comparative efficacy of the two drugs in improving symptoms in patients with chronic schizophrenia. ObjectiveTo compare the efficacy of aripiprazole and risperidone on the improvement of symptoms， prepulse inhibition （PPI）， cognitive functioning and neurotrophic factors in patients with chronic schizophrenia， so as to provide effective treatment regimens for these patients. MethodsA total of 86 patients with chronic schizophrenia attending the psychiatry department of the Third People's Hospital of Fuyang from March 2021 to March 2023 and fulfilling the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） were enrolled and grouped using random number table method， each with 43 cases. Aripiprazole group was given oral aripiprazole once daily at an initial dose of 5 mg for one week and then gradually increased to a maximum dose of 25 mg. Risperidone group received oral risperidone twice daily at an initial dose of 0.5 mg for one week and then gradually increased to a maximum dose of 3 mg. Treatment in both groups lasted 3 months. Before treatment and 3 months after treatment， Patients were required to complete Positive and Negative Symptom Scale （PANSS）， detection of both strong and weak PPIs in a startle modification passive attention paradigm， Wisconsin Card Sorting Test （WCST） and the measurement of neurotrophic factors at baseline and after treatment. The adverse reactions were recorded. Analysis of covariance was used to test the difference between the PANSS score， PPI， WCST and neurotrophic factor levels of the groups， with the pretest used as the covariate. Results3 months after treatment， no statistical difference was found in the scores of PANSS general psychopathology subscale， positive symptom subscale， negative symptom subscale and total score between two groups after treatment （F=0.621， 0.815， 0.743， 0.752， P>0.05）. There were no statistically significant differences between the two groups in PPI inhibition rate， single intense stimulus amplitude， single intense stimulus latency， prepulse inhibition amplitude， or prepulse inhibition latency （F=0.174， 0.001， 0.183， 0.171， 0.001， P>0.05）. There was no statistically significant difference in the total number of WCST tests between two groups （F=0.512， P>0.05）， whereas aripiprazole group reported significantly larger total numbers of categories completed and correct responses as well as smaller total numbers of random errors and perseverative errors compared to risperidone group （F=3.737， 4.621， 4.892， 5.130， P<0.05）. A significant increase in brain-derived neurotrophic factor （BDNF） and nerve growth factor （NGF） along with a reduction in glial fibrillary acidic protein （GFAP） were documented in risperidone group when compared to risperidone group （F=4.414， 3.781， 6.319， P<0.05）. No significant difference was demonstrated in the incidence of adverse reactions between the two groups （χ²=0.261， P>0.05）. ConclusionAripiprazole may be more beneficial than risperidone in improving cognitive functioning and neurotrophic factor levels in patients with chronic schizophrenia. ［Funded by Scientific Research Project of Fuyang Municipal Health Commission in 2021 （number， FY2021-147）］