Objective:To understand the incidence trend of brucellosis over time in Shandong Province from 2004 to 2023, and provide evidence for the prevention and control of brucellosis.Methods:The incidence data of brucellosis in Shandong from 2004 to 2023 were collected from China Disease Prevention and Control Information System. The annual change percentage (APC) and annual average change percentage (AAPC) of the incidence rate were calculated by using Joinpoint regression model. A age-period-cohort model was used to analyze changes in brucellosis incidence with age, period, and birth cohort.Results:The average annual incidence of brucellosis was 1.76/100 000 in Shandong from 2004 to 2023. The Joinpoint regression analysis results showed that the reported incidence of brucellosis increased by an average of 92.0% and 18.9% each year from 2004 to 2010 and from 2010 to 2014, respectively, and decreased by an average of 0.2% each year from 2014 to 2023. The results of APC model showed that the incidence of brucellosis increased first and then decreased with age ( χ2=176.92, P<0.001), and incidence of brucellosis showed slow increase and rapid increase first, then decrease ( χ2=2 921.03, P<0.001) over time. The risk for brucellosis reached peak in 2016 ( RR=5.29, 95% CI: 4.96-5.65) and became the lowest in 2006 ( RR=0.24, 95% CI: 0.21-0.28). The incidence increased in later birth cohort ( χ2=348.88, P<0.001), the AAPCs of all the age groups were between 15.0% and 40.0%, and the older the age, the greater the risk ( χ2=348.77, P<0.001). Conclusions:From 2004 to 2023, the reported incidence of brucellosis in Shandong showed a significant age-period-cohort effect, which increased first and then decreased, first increased and then decreased with age, increased slowly and rapidly first, then decreased over time, and increased in later birth cohort. It is necessary to conduct targeted prevention and control, health education to reduce the risk for brucellosis.

Objective To investigate the factors influencing the natural outcome of low-grade squamous intraepithelial lesions(LSIL)of the cervix.Methods A total of 154 patients who underwent colposcopic cervical biopsy in the Third Affiliated Hospital of Zhengzhou University from January 2022 to January 2023 were selected and divided into negative conversion group(55 cases),continuous group(70 cases)and upgraded group(29 cases)according to the follow-up results.Logistic regression was used to analyze the influence of related factors on the outcome of LSIL.Results There were statistically significant differences in the number of vaginal births,the results of thin-prep cytology test,human papilloma virus(HPV)typing,whether vaginal LSIL was combined,whether there were symptoms,and vaginal microecology among three groups(P＜0.05).Multivariate Logistic analysis showed that combined vaginal LSIL,vaginal microecological abnormalities,atypical squamous cell-cannot exclude high-grade squamous intraepithelial lesion(ASC-H)/high-grade squamous intraepithelial lesion(HSIL),HPV 16/18 positive or mixed positive were independent risk factors for persistent infection(P＜0.05),combined vaginal LSIL,symptomatic,vaginal microecological abnormalities,ASC-H/HSIL,HPV 16/18 positive or mixed positive were all independent risk factors for escalation of lesions(P＜0.05).Conclusion Patients with vaginal LSIL,vaginal microecological abnormalities,ASC-H/HSIL,HPV 16/18 positive or mixed positive should be followed up and early intervention to reduce the risk of disease escalation.

Objective To investigate the factors influencing the natural outcome of low-grade squamous intraepithelial lesions(LSIL)of the cervix.Methods A total of 154 patients who underwent colposcopic cervical biopsy in the Third Affiliated Hospital of Zhengzhou University from January 2022 to January 2023 were selected and divided into negative conversion group(55 cases),continuous group(70 cases)and upgraded group(29 cases)according to the follow-up results.Logistic regression was used to analyze the influence of related factors on the outcome of LSIL.Results There were statistically significant differences in the number of vaginal births,the results of thin-prep cytology test,human papilloma virus(HPV)typing,whether vaginal LSIL was combined,whether there were symptoms,and vaginal microecology among three groups(P＜0.05).Multivariate Logistic analysis showed that combined vaginal LSIL,vaginal microecological abnormalities,atypical squamous cell-cannot exclude high-grade squamous intraepithelial lesion(ASC-H)/high-grade squamous intraepithelial lesion(HSIL),HPV 16/18 positive or mixed positive were independent risk factors for persistent infection(P＜0.05),combined vaginal LSIL,symptomatic,vaginal microecological abnormalities,ASC-H/HSIL,HPV 16/18 positive or mixed positive were all independent risk factors for escalation of lesions(P＜0.05).Conclusion Patients with vaginal LSIL,vaginal microecological abnormalities,ASC-H/HSIL,HPV 16/18 positive or mixed positive should be followed up and early intervention to reduce the risk of disease escalation.

Objective:To understand the incidence trend of brucellosis over time in Shandong Province from 2004 to 2023, and provide evidence for the prevention and control of brucellosis.Methods:The incidence data of brucellosis in Shandong from 2004 to 2023 were collected from China Disease Prevention and Control Information System. The annual change percentage (APC) and annual average change percentage (AAPC) of the incidence rate were calculated by using Joinpoint regression model. A age-period-cohort model was used to analyze changes in brucellosis incidence with age, period, and birth cohort.Results:The average annual incidence of brucellosis was 1.76/100 000 in Shandong from 2004 to 2023. The Joinpoint regression analysis results showed that the reported incidence of brucellosis increased by an average of 92.0% and 18.9% each year from 2004 to 2010 and from 2010 to 2014, respectively, and decreased by an average of 0.2% each year from 2014 to 2023. The results of APC model showed that the incidence of brucellosis increased first and then decreased with age ( χ2=176.92, P<0.001), and incidence of brucellosis showed slow increase and rapid increase first, then decrease ( χ2=2 921.03, P<0.001) over time. The risk for brucellosis reached peak in 2016 ( RR=5.29, 95% CI: 4.96-5.65) and became the lowest in 2006 ( RR=0.24, 95% CI: 0.21-0.28). The incidence increased in later birth cohort ( χ2=348.88, P<0.001), the AAPCs of all the age groups were between 15.0% and 40.0%, and the older the age, the greater the risk ( χ2=348.77, P<0.001). Conclusions:From 2004 to 2023, the reported incidence of brucellosis in Shandong showed a significant age-period-cohort effect, which increased first and then decreased, first increased and then decreased with age, increased slowly and rapidly first, then decreased over time, and increased in later birth cohort. It is necessary to conduct targeted prevention and control, health education to reduce the risk for brucellosis.

ObjectiveTo investigate the effects of Bushen Huoxue prescription on the cardiac function， inflammation， and quality of life of the patients with chronic heart failure resistant to diuretics. MethodA total of 78 patients who met the inclusion criteria were randomized into observation and control groups （39 cases）. Both groups received standardized treatment for diuretic resistance in accordance with the guidelines. In addition， the observation group received Bushen Huoxue prescription. The cardiac function indicators， total response rate regarding symptom alleviation， exercise endurance， urine volume， body mass， quality of life， and levels of inflammatory cytokines were compared between the two groups before and after treatment. ResultBefore treatment， the two groups of patients showed no significant differences in terms of 24 h urine volume， body mass， 6 minute walk test （6MWT）， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP） level， left ventricular ejection fraction （LVEF）， stroke volume （SV）， and serum levels of interleukin-6 （IL-6）， interleukin-4 （IL-4）， and tumor necrosis factor-alpha （TNF-α）. After treatment， the observation group outperformed the control group in terms of the response rates regarding traditional Chinese medicine symptom scores and New York Heart Association （NYHA） grading of cardiac function （P<0.05）. After treatment， the body mass， MLHFQ score， and IL-6， TNF-α， and NT-proBNP levels decreased in both groups （P<0.05， P<0.01）， and the observation group showed more significant decreases than the control group （P<0.05， P<0.01）. Both groups showed increases in 24-h urine volume， 6MWT， LVEF， SV， and IL-4 after treatment （P<0.05， P<0.01）， and the observation group showed more significant increases than the control group （P<0.05， P<0.01）. ConclusionThe combination of Bushen Huoxue prescription with standardized treatment is effective in ameliorating the clinical symptoms of the patients with chronic heart failure resistant to diuretics. Moreover， it alleviates diuretic resistance and improves the cardiac function without causing obvious adverse reactions.

ObjectiveTo explore the clinical efficacy of Huangjin Shuangshen Jiawei （HJSSJW） granules in treating postoperative anxiety and depression after percutaneous coronary intervention （PCI） for coronary heart disease and the effects of this medicine on inflammatory cytokines. MethodNinety-four patients diagnosed with anxiety and depression after PCI were randomized into observation and control groups （47 cases） by the double-blind method. On the basis of conventional Western medical treatment， the observation group was treated with HJSSJW granules for 12 weeks， and the control group with the simulant of HJSSJW granules for 12 weeks. The two groups were compared in terms of Hamilton Anxiety and Depression Scales （HAMA-14， HAMD-24）， Pittsburgh Sleep Quality Inventory （PSQI）， Seattle Angina Score （SAQ）， TCM symptom scores， traditional Chinese medicine （TCM） symptom score and response rate， serum levels of hypersensitive-C reactive protein （hs-CPR）， tumor necrosis factor （TNF）-α， and interleukin （IL-6）， and incidence of major adverse cardiovascular events （MACEs） and adverse reactions. ResultAfter treatment， both groups showed declined scores of HAMA-14， HAMD-24， and PSQI （P<0.05， P<0.01） and the observation group had lower scores of HAMA-14， HAMD-24， and PSQI than the control group （P<0.01）. The scores of SAQ in both groups increased after treatment （P<0.01）， and the observation group had higher score of each dimension than the control group （P<0.05）. The TCM symptom scores decreased in both groups after treatment （P<0.01）， and they were lower in the observation group than in the control group （P<0.05）. The total response rate regarding TCM symptoms in the observation group was higher than that in the control group （χ²=9.225， P<0.01）. After treatment， the levels of hs-CPR， IL-6， and TNF-α became lowered in both groups （P<0.01）， and the observation group had lower levels of hs-CPR， IL-6， and TNF-α than the control group （P<0.05）. The incidence of MACEs in the observation group was lower than that in the control group during the 90 d of the follow-up period （χ²=4.242， P<0.05）. No adverse reactions associated with the use of HJSSJW granules were observed during the trial period. ConclusionHJSSJW granules can alleviate the bad mood， improve sleep， mitigate somatic symptoms， improve the quality of life， reduce inflammatory damage， and improve prognosis， being safe for clinical use in patients with postoperative anxiety and depression after PCI for coronary heart disease.

BACKGROUND:Tissue engineering has brought new hope to the clinical challenge of liver failure,and the preparation of plant-derived decellularized fiber scaffolds holds significant importance in liver tissue engineering. OBJECTIVE:To prepare apple tissue decellularized scaffold material by using fresh apple slices and a solution of sodium dodecyl sulfate,and assess its biocompatibility. METHODS:Fresh apples were subjected to decellularization using phosphate buffer saline and sodium dodecyl sulfate solution,separately.Afterwards,the decellularized apple tissues and apple decellularized scaffold materials were decontaminated with phosphate buffer saline.Subsequently,scanning electron microscopy was used to assess the effectiveness of decellularization of the apple materials.Adipose-derived mesenchymal stem cells were extracted from the inguinal fat BALB/C of mice,and their expression of stem cell-related markers(CD45,CD34,CD73,CD90,and CD105)was identified through flow cytometry.The cells were then divided into a scaffold-free control group and a scaffold group.Equal amounts of adipose-derived mesenchymal stem cells were seeded onto both groups.The biocompatibility of the decellularized scaffold with adipose-derived mesenchymal stem cells was evaluated using CCK-8 assay,hematoxylin-eosin staining,and phalloidine staining.Cell adhesion and growth on the scaffold were observed under light microscopy and scanning electron microscopy.Furthermore,the scaffold was subdivided into the non-induced group and the hepatogenic-induced group.Adipose-derived mesenchymal stem cells were cultured on the decellularized apple scaffold,and they were cultured for 14 days in regular culture medium or hepatogenic induction medium for comparison.Immunofluorescent staining using liver cell markers,including albumin,cytokeratin 18,and CYP1A1,was performed.Enzyme-linked immunosorbent assay was used to detect the secretion of alpha fetoprotein and albumin.Additionally,scanning electron microscopy was employed to observe the morphology of the induced cells on the scaffold,verifying the expression of liver cell-related genes on the decellularized scaffold material.Finally,the cobalt-60 irradiated and sterilized decellularized apple scaffolds were transplanted onto the surface of mouse liver and the degradation of the scaffold was observed by gross observation and hematoxylin-eosin staining after 28 days. RESULTS AND CONCLUSION:(1)The scanning electron microscopy results revealed that the decellularized apple scaffold material retained a porous structure of approximately 100 μm in size,with no residual cells observed.(2)Through flow cytometry analysis,the cultured cells were identified as adipose-derived mesenchymal stem cells.(3)CCK-8 assay results demonstrated that the prepared decellularized apple tissue scaffold material exhibited no cytotoxicity.Hematoxylin-eosin staining and phalloidine staining showed that adipose-derived mesenchymal stem cells were capable of adhering and proliferating on the decellularized apple tissue scaffold.(4)The results obtained from immunofluorescence staining and enzyme-linked immunosorbent assay revealed that adipose-derived mesenchymal stem cells cultured on the decellularized apple scaffolds exhibited elevated expression of liver-specific proteins,including albumin,alpha-fetoprotein,cytokeratin 18,and CYP1A1.These results suggested that they were induced differentiation into hepatocyte-like cells possessing functional characteristics of liver cells.(5)The decellularized apple scaffold implanted at 7 days has integrated with the liver,with partial degradation of the scaffold observed.By 28 days,the decellularized apple scaffold has completely degraded and has been replaced by newly-formed tissue.(6)The results indicate that the decellularized scaffold material derived from apple tissue demonstrates favorable biocompatibility,promoting the proliferation,adhesion,and hepatic differentiation of adipose-derived mesenchymal stem cells.

Objective:To investigate the potential source of infection for a cluster outbreak of human brucellosis in Yantai City, Shandong Province.Methods:The information of a human brucellosis cluster outbreak case in Yantai City, Shandong Province in 2022 was collected, the strains were isolated and cultured, and DNA was extracted. BCSP31-PCR was used for species identification, and AMOS-PCR was used for species type identification. Multiple locus variable-number tandem-repeat analysis (MLVA)-16 was used for clustering analysis, and the results were compared with the public database MLVAbank and the monitoring data of Brucella in Shandong Province in 2022. At the same time, whole genome single nucleotide polymorphism (wgSNP) typing was used to analyze the 53 Brucella strains that had completed whole genome sequencing in Shandong Province in 2022, and the wgSNP phylogenetic tree was constructed. Results:According to BCSP31-PCR and AMOS-PCR identification, the three strains related to the cluster outbreak of brucellosis in Yantai City, Shandong Province in 2022 were all Brucella melitensis biotype. The results of MLVA-16 typing showed that the MLVA-16 typing of the three isolated strains was completely consistent, with 16 tandem repeat loci of 1-5-3-13-2-2-3-2-4-41-8-4-4-3-6-5, belonging to the Eastern Mediterranean clade. Compared with MLVAbank, the MLVA-16 typing of two strains isolated from Kazakhstan was consistent with the results of this study. Compared with the monitoring data of Brucella in Shandong Province in 2022, it was found that the MLVA-16 typing of 11 isolated strains was consistent with the results of this study, which were isolated from Zaozhuang, Linyi, Taian, Yantai, and Weifang cities, respectively. The results of wgSNP typing showed that the distance between the 11 strains and the strains of the current outbreak was less than 7 single nucleotide polymorphisms, and the strains were isolated from Taian, Zibo, Linyi, Binzhou, Jinan, Jining, Yantai and Weihai cities, respectively. Conclusion:After tracing the source of a human brucellosis cluster outbreak in Yantai City, Shandong Province in 2022, it is speculated that the strains of Brucella melitensis isolated from Linyi, Taian and Yantai cities are closely related, indicating that sheep in these areas have homology.

Objective:To evaluate the efficacy and safety of mosapride citrate dispersible tablet (MP) combined with Shugan Jieyu capsule (SGJY) in the treatment of functional dyspepsia (FD).Methods:From April 2018 to January 2019, FD patients from 10 hospitals including Renji Hospital, Shanghai Jiaotong University School of Medicine, Luohe Hospital of Traditional Chinese Medicine, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Handan Hospital of Traditional Chinese Medicine and Nanshi Hospital of Nanyang were selected for a randomized, double-blind, placebo-controlled trial. The patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder-7 (GAD-7) were used to assess depression and anxiety in FD patients, respectively. According to the random number table method, 200 FD patients who met the inclusion criteria were randomly divided into SGJY+ MP group and placebo+ MP group, with 100 patients in each group, and all the patients were given oral MP. The patients of the SGJY+ MP group and the placebo+ MP group were given oral SGJY or placebo on the basis of MP, respectively. The patients of both groups were treated continuously for 6 weeks. Total FD symptom scores, PHQ-9 and GAD-7 scores, as well as efficiency and safety were evaluated after treatment. Independent samples t-test and chi-square test were used for statistical analysis. Results:A total of 193 patients were included into the full analysis set with 94 cases in the SGJY+ MP group and 99 cases in the placebo+ MP group. A total of 183 patients completed the 6-week trial, including 89 cases in the SGJY+ MP group and 94 cases in the placebo+ MP group. A total of 198 patients were included in the safety analysis set, including 99 cases in the SGJY+ MP group and 99 cases in the placebo+ MP group.After treatment, the total FD symptom scores of the SGJY+ MP group and the placebo+ MP group were both lower than those of baseline before treatment (3.71±3.06 vs. 11.79±5.18 and 4.17±3.69 vs. 11.19±5.05), and the differences were both statistically significant ( t=-24.87 and -23.27, both P<0.001). The efficacy of the SGJY+ MP group was higher than that of the placebo+ MP group (86.5%, 77/89 vs. 74.5%, 70/94), and the difference was statistically significant ( χ2=4.69, P=0.030). The efficacy of patients with moderate-to-severe anxiety and depression in the SGJY+ MP group was both higher than that of patients in the placebo+ MP group (10/10 vs. 3/7, 85.0%, 17/20 vs. 8/14), and the differences were statistically significant ( χ2=5.66 and 5.33, P=0.017 and 0.010). The efficacy of patients with postprandial distress syndrome (PDS) subtype in the SGJY+ MP group was higher than that of patients in the placebo+ MP group (93.0%, 53/57 vs. 76.5%, 39/51), and the difference was statistically significant (χ 2=5.82, P=0.016). The PHQ-9 scores of patients with depression in both SGJY+ MP and placebo+ MP groups were lower than those at baseline before treatment (3.63±2.76 vs. 7.87±2.24 and 3.35±2.51 vs. 7.63±2.25), and the differences were statistically significant ( t=-14.88 and -15.87, both P<0.001). There was no significant difference in proportion of depressed patients with a ≥50% reduction in PHQ-9 scores from baseline value between the SGJY+ MP group and the placebo+ MP group (60.2%, 50/83 vs. 62.8%, 54/86; χ2=0.05, P=0.825). The GAD-7 scores of anxious patients both the SGJY+ MP group and the placebo+ MP group were lower than the baseline value before treatment (3.27±2.57 vs. 7.09±2.08 and 3.86±2.49 vs. 6.84±1.66), and the differences were statistically significant ( t=-13.30 and -11.47, both P<0.001). The proportion of anxious patients with a ≥50% reduction in GAD-7 scores from baseline in the SGJY+ MP group was higher than that of the placebo+ MP group (54.4%, 43/79 vs. 36.5%, 27/74), and the difference was statistically significant ( χ2=4.53, P=0.033). There were no serious adverse events in both the SGJY+ MP group and the placebo+ MP group during the treatment. There were no significant differences in the incidence of adverse events and adverse reactions during the treatment between the SGJY+ MP group and the placebo+ MP group (7.1%, 7/99 vs. 5.1%, 5/99, and 3.0%, 3/99 vs. 3.0%, 3/99, respectively; both P>0.05). Conclusion:SGTY can safely and effectively improve the efficacy of the prokinetic drugs in the treatment of FD symptoms, especially in FD patients with PDS subtype or with moderate-to-severe anxiety and with depression.

Objective:To evaluate the efficacy and safety of mosapride citrate dispersible tablet (MP) combined with Shugan Jieyu capsule (SGJY) in the treatment of functional dyspepsia (FD).Methods:From April 2018 to January 2019, FD patients from 10 hospitals including Renji Hospital, Shanghai Jiaotong University School of Medicine, Luohe Hospital of Traditional Chinese Medicine, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Handan Hospital of Traditional Chinese Medicine and Nanshi Hospital of Nanyang were selected for a randomized, double-blind, placebo-controlled trial. The patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder-7 (GAD-7) were used to assess depression and anxiety in FD patients, respectively. According to the random number table method, 200 FD patients who met the inclusion criteria were randomly divided into SGJY+ MP group and placebo+ MP group, with 100 patients in each group, and all the patients were given oral MP. The patients of the SGJY+ MP group and the placebo+ MP group were given oral SGJY or placebo on the basis of MP, respectively. The patients of both groups were treated continuously for 6 weeks. Total FD symptom scores, PHQ-9 and GAD-7 scores, as well as efficiency and safety were evaluated after treatment. Independent samples t-test and chi-square test were used for statistical analysis. Results:A total of 193 patients were included into the full analysis set with 94 cases in the SGJY+ MP group and 99 cases in the placebo+ MP group. A total of 183 patients completed the 6-week trial, including 89 cases in the SGJY+ MP group and 94 cases in the placebo+ MP group. A total of 198 patients were included in the safety analysis set, including 99 cases in the SGJY+ MP group and 99 cases in the placebo+ MP group.After treatment, the total FD symptom scores of the SGJY+ MP group and the placebo+ MP group were both lower than those of baseline before treatment (3.71±3.06 vs. 11.79±5.18 and 4.17±3.69 vs. 11.19±5.05), and the differences were both statistically significant ( t=-24.87 and -23.27, both P<0.001). The efficacy of the SGJY+ MP group was higher than that of the placebo+ MP group (86.5%, 77/89 vs. 74.5%, 70/94), and the difference was statistically significant ( χ2=4.69, P=0.030). The efficacy of patients with moderate-to-severe anxiety and depression in the SGJY+ MP group was both higher than that of patients in the placebo+ MP group (10/10 vs. 3/7, 85.0%, 17/20 vs. 8/14), and the differences were statistically significant ( χ2=5.66 and 5.33, P=0.017 and 0.010). The efficacy of patients with postprandial distress syndrome (PDS) subtype in the SGJY+ MP group was higher than that of patients in the placebo+ MP group (93.0%, 53/57 vs. 76.5%, 39/51), and the difference was statistically significant (χ 2=5.82, P=0.016). The PHQ-9 scores of patients with depression in both SGJY+ MP and placebo+ MP groups were lower than those at baseline before treatment (3.63±2.76 vs. 7.87±2.24 and 3.35±2.51 vs. 7.63±2.25), and the differences were statistically significant ( t=-14.88 and -15.87, both P<0.001). There was no significant difference in proportion of depressed patients with a ≥50% reduction in PHQ-9 scores from baseline value between the SGJY+ MP group and the placebo+ MP group (60.2%, 50/83 vs. 62.8%, 54/86; χ2=0.05, P=0.825). The GAD-7 scores of anxious patients both the SGJY+ MP group and the placebo+ MP group were lower than the baseline value before treatment (3.27±2.57 vs. 7.09±2.08 and 3.86±2.49 vs. 6.84±1.66), and the differences were statistically significant ( t=-13.30 and -11.47, both P<0.001). The proportion of anxious patients with a ≥50% reduction in GAD-7 scores from baseline in the SGJY+ MP group was higher than that of the placebo+ MP group (54.4%, 43/79 vs. 36.5%, 27/74), and the difference was statistically significant ( χ2=4.53, P=0.033). There were no serious adverse events in both the SGJY+ MP group and the placebo+ MP group during the treatment. There were no significant differences in the incidence of adverse events and adverse reactions during the treatment between the SGJY+ MP group and the placebo+ MP group (7.1%, 7/99 vs. 5.1%, 5/99, and 3.0%, 3/99 vs. 3.0%, 3/99, respectively; both P>0.05). Conclusion:SGTY can safely and effectively improve the efficacy of the prokinetic drugs in the treatment of FD symptoms, especially in FD patients with PDS subtype or with moderate-to-severe anxiety and with depression.