BACKGROUND:Several studies have found that the total flavonoids of rhizome drynariae can promote neovascularization in the induced membrane,improve the biological properties of the induced membrane,and accelerate bone remodeling in the induced membrane,but the related molecular mechanisms still need to be further explored. OBJECTIVE:To explore the effect of total flavonoids of rhizome drynariae on bone remodeling in rat femoral Masquelet-induced membrane model by regulating H-type blood vessels. METHODS:Thirty-six male Sprague-Dawley rats were stratified by body mass and then randomly divided into blank group,model group and traditional Chinese medicine group,with 12 rats in each group.A 4-mm femoral bone defect model was established in all the rats.Bone defects in the model group and traditional Chinese medicine group were filled with polymethylmethacrylate bone cement.At 6 weeks after modeling,the tail bone of the rats was implanted in the blank group,as well as in the other two groups after removal of bone cement.The traditional Chinese medicine group was given 157.5 mg/kg per day of total flavonoids of rhizome drynariae at 3 days after bone implantation,while the model and blank groups were given the same amount of saline by gavage until the 8th week after bone implantation.Bone graft samples were taken for relevant testing at 8 weeks after implantation. RESULTS AND CONCLUSION:X-ray films showed that in the blank group,the fracture line in the defect area was clear,and only a small amount of bone callus formed;in the model group,the bone defect area still existed,where discontinuous cortical bone was visible;in the traditional Chinese medicine group,the defect area was filled with newborn bone tissues,the bone marrow cavity and part of the cortical bone formed,and the fracture line disappeared.Micro-CT scans showed that the amount of new bone in the defect area was low in the blank group,the number of bone trabeculae in the defect area was significantly increased in the model group,and a large amount of new bone tissue was filled in the bone defect area in the traditional Chinese medicine group.Hematoxylin-eosin staining results showed that in the blank group,only a small amount of new bone formed in the defect area and the quality of osteogenesis was poor;in the model group,there was more new bone tissue in the defect area,but some fibrous connective tissues were interspersed within the bone tissue;and in the traditional Chinese medicine group,a large amount of new bone formed in the defect area and the quality of osteogenesis was the best.CD31/Emcn immunofluorescence double-labeling staining results showed that the number of H-type blood vessels in the newborn bone tissue in the bone defect area of the blank group was sparse and sparsely distributed;compared with the blank group,there were more H-type blood vessels in the bone tissue in the bone defect area of the model group,and the blood vessels were distributed in relatively regular strips;the number of H-type blood vessels in the bone defect area of the traditional Chinese medicine group was the highest and the blood vessels were densely distributed.To conclude,the total flavonoids of rhizoma drynariae can upregulate the expression of H-type blood vessels to enhance the angiogenic-osteogenic effect,improve the osteogenic efficiency of the rat femoral Masquelet induced membrane model,and promote bone remodeling.

OBJECTIVE To explore the protective effects and potential mechanisms of Hirudo on mice with non-alcoholic fatty liver disease （NAFLD） in mice. METHODS The male ApoE－/－ mice were randomly divided into the model group and Hirudo low- dose and high-dose groups （0.45， 0.9 g/kg）， with 10 mice in each group； another 10 wild-type male C57BL/6J mice were chosen as the control group. The control group was fed with basal maintenance chow and the remaining groups were fed with high-fat chow for 12 weeks to establish the NAFLD model. Each administration group was given corresponding solution intragastrically， once a day， for 8 consecutive weeks. In the 13th week， the body weight and liver weight of mice in each group were measured after the last medication， and the liver index was calculated； the serum levels of nuclear factor-κB （NF-κB）， tumor necrosis factor-α （TNF- α）， interleukin-1β （IL-1β）， IL-6， total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C） were detected； the liver pathomorphological changes were observed； the protein expressions of peroxisome proliferator-activated receptor γ（PPARγ） and silence information regulator type 1 （SIRT1） were detected. RESULTS Compared with the control group， the liver tissue of mice in the model group showed more fat vacuoles and infiltration of inflammatory cells， with significant lipid accumulation； the body weight， liver weight and liver index of the mice， and serum levels of NF-κB， TNF-α， IL-1β， IL-6， TC， TG and LDL-C significantly increased， while the serum level of HDL-C， the protein expressions of PPARγ and SIRT1 in liver tissues significantly decreased （P＜0.01）. Compared with the model group， the pathological changes in liver tissue of mice were all relieved in Hirudo low-dose and high-dose groups； the body weight， liver weight and liver index， the serum levels of NF-κB， TNF-α， IL-1β， IL-6， TC， TG and LDL-C decreased significantly， while the serum level of HDL-C， the protein expressions of PPARγ and SIRT1 in liver tissue all increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Hirudo can regulate liver lipid metabolism and inhibit inflammation by activating the protein expressions of PPARγ and SIRT1， thus having a significant ameliorative effect on NAFLD.

Background::Breast cancer is ranked among the most prevalent malignancies in the Chinese female population. However, comprehensive reports detailing the latest epidemiological data and attributable disease burden have not been extensively documented.Methods::In 2018, high-quality cancer surveillance data were recorded in 700 population-based cancer registries in China. We extracted data on female breast cancers (International Classification of Diseases, Tenth Revision [ICD-10]: C50) and estimated the incidence and mortality in 2022 according to the baseline data and corresponding trends from 2010 to 2018. Pathological types were classified according to the ICD for Oncology, 3rd Edition codes. Disability-adjusted life years (DALYs) were calculated as the sum of the years of life lost (YLLs) and years lived with disability (YLDs).Results::In 2022, approximately 357,200 new female breast cancer cases and 75,000 deaths occurred in China, accounting for 15.59% and 7.94% of total new cancer cases and deaths, respectively. The age-standardized incidence rate (ASIR) was 33.04 per 100,000. When analyzed by pathological type, the ASIRs for papillary neoplasms, invasive breast carcinoma, rare and salivary gland-type tumors, and other types were 1.13, 29.79, 0.24, and 1.88 per 100,000, respectively. The age-standardized mortality rate (ASMR) was 6.10 per 100,000. A total of 2,628,000 DALYs were found to be attributable to female breast cancer in China, comprising 2,278,300 YLLs and 349,700 YLDs. The ASIR, ASMR, and age-standardized rate (ASR) for DALYs in urban areas were consistently higher than those in rural areas. We observed a four-fold increase in the ASIR and ASR for DALYs and an eight-fold increase in the ASMR among females over 55 years compared with those aged under 55 years.Conclusion::These data provide invaluable insights into the latest epidemiology of female breast cancer in China and highlight the urgency for disease prevention and control strategy formulation.

Objective To explore the predictive value of combined detection of immunoglobulin binding protein 1 (IGBP 1) in serum and urine in lupus nephritis (LN). Methods A total of 60 LN patients were selected as LN group, and 60 SLE erythematosus (SLE) patients in the same period were selected as SLE group, the serum IGBP 1 and urinary IGBP 1 levels between the two groups were compared, and the value of serum IGBP 1, urinary IGBP 1 and their combination in predicting LN was analyzed. Results Serum IGBP 1 and urinary IGBP 1 in the LN group were significantly higher than those in the SLE group (P < 0.05). Binary Logistic regression analysis showed that serum IGBP 1 and urinary IGBP 1 were risk factors for LN (P < 0.05). Receiver Operating Characteristic (ROC) curve revealed that the area under the curve (AUC) for serum IGBP1, urinary IGBP1, and their combined detection for LN was 0.856, 0.834, and 0.902, respectively. The Youden index was 0.533, 0.533, and 0.666, respectively. The sensitivity and specificity of serum IGBP1 were 85.0% and 68.3%, respectively. The sensitivity and specificity of urinary IGBP1 were 53.3% and 100.0%, respectively. The sensitivity and specificity of the combined detection were 78.3% and 88.3%, respectively. Conclusion Serum IGBP 1 and urinary IGBP 1 are highly expressed in LN patients, and their combination has a high predictive value for LN.

OBJECTIVE: To develop a drug-loaded composite microsphere that can simultaneously release the berberine (BBR) and naringin (NG) to repair infectious bone defects. METHODS: The NG was loaded on mesoporous microspheres (MBG) to obtain the drug-loaded microspheres (NG-MBG). Then the dual drug-loaded compound microspheres (NG-MBG@PDA-BBR) were obtained by wrapping NG-MBG with polydopamine (PDA) and modifying the coated PDA with BBR. The composite microspheres were characterized by scanning electron microscopy, X-ray diffraction, specific surface area and pore volume analyzer, and Fourier transform infrared spectroscopy; the drug loading rate and release of NG and BBR were measured; the colony number was counted and the bacterial inhibition rate was calculated after co-culture with Staphylococcus aureus and Escherichia coli for 12 hours to observe the antibacterial effect; the biocompatibility was evaluated by live/dead cell fluorescence staining and cell counting kit 8 assay after co-culture with rat's BMSCs for 24 and 72 hours, respectively, and the osteogenic property was evaluated by alkaline phosphatase (ALP) staining and alizarin red staining after 7 and 14 days, respectively. RESULTS: NG-MBG@PDA-BBR and three control microspheres (MBG, MBG@PDA, and NG-MBG@PDA) were successfully constructed. Scanning electron microscopy showed that NG-MBG@PDA-BBR had a rough lamellar structure, while MBG had a smooth surface, and MBG@PDA and NG-MBG@PDA had a wrapped agglomeration structure. Specific surface area analysis showed that MBG had a mesoporous structure and had drug-loading potential. Low angle X-ray diffraction showed that NG was successfully loaded on MBG. The X-ray diffraction pattern contrast showed that all groups of microspheres were amorphous. Fourier transform infrared spectroscopy showed that NG and BBR peaks existed in NG-MBG@PDA-BBR. NG-MBG@PDA-BBR had good sustained drug release ability, and NG and BBR had early burst release and late sustained release. NG-MBG@PDA-BBR could inhibit the growth of Staphylococcus aureus and Escherichia coli, and the antibacterial ability was significantly higher than that of MBG, MBG@PDA, and NG-MBG@PDA ( P<0.05). But there was a significant difference in biocompatibility at 72 hours among microspheres ( P<0.05). ALP and alizarin red staining showed that the ALP positive area and the number of calcium nodules in NG-MBG@PDA-BBR were significantly higher than those of MBG and NG-MBG ( P<0.05), and there was no significant difference between NG-MBG@PDA and NG-MBG@PDA ( P>0.05). CONCLUSION NG-MBG@PDA-BBR have sustained release effects on NG and BBR, indicating that it has ideal dual performance of osteogenesis and antibacterial property.
Rats ; Animals ; Osteogenesis ; Delayed-Action Preparations/pharmacology* ; Microspheres ; Berberine/pharmacology* ; Anti-Bacterial Agents/pharmacology* ; Escherichia coli

Objective:To evaluate the performance of rural practitioners of endoscopic cleaning and disinfection participating in the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers and to analyze the influencing factors.Methods:The questionnaires for skill assessment were designed based on the skill scheme and clinical practice of the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers in rural China, and the App Early diagnosis, Early treatment was used as the examination platform. The practitioners in 539 county hospitals from 25 provinces participating in the program in 2019 were assessed for techniques and skills for endoscopic cleaning and disinfection and the excellence rate was calculated. Multivariate logistic regression model was used to analyze the influencing factors for the examination. Results:A total of 1 671 endoscopic cleaning and disinfection practitioners participated in the assessment with the score of 73.41±16.60. The passing rate was 85.82%, and the excellence rate was 44.94%. Among all questions, the correct rate of "opportunistic screening flow chart" was the highest (98.21%), and that of "the evaluation index for mass screening" was the lowest (57.89%). The multivariate logistic regression analysis showed that the excellence rate was high in practitioners who had a bachelor degree or above ( OR=1.627,95% CI:1.319-2.007, P<0.001), the career for 5 to <15 years (5 to <10 years: OR=1.329,95% CI:1.045-1.689, P=0.020; 10 to <15 years: OR=1.384,95% CI:1.026-1.867, P=0.033), working in eastern and central regions (eastern regions: OR=3.476,95% CI:2.368-5.103, P<0.001;central regions: OR=4.028,95% CI:2.679-6.057, P<0.001) and with full understanding of the screening scheme ( OR=1.547,95% CI:1.246-1.921, P<0.001) . Conclusion:Practitioners on the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers in rural China have mastered the basic screening scheme and skills for endoscopic cleaning and disinfection. The education background, duration of the career, area and understanding of screening scheme are influencing factors for the excellence rate of endoscopic cleaning and disinfection.

Humans ; Vaccines, Inactivated ; COVID-19/prevention & control* ; Vaccination ; Viral Vaccines ; Immunity ; Antibodies, Viral

ObjectiveTo screen and establish animal models of combined stasis and toxin syndrome based on the comparison of three modeling methods， i.e.， carrageenan （Ca）， Ca combined with dried yeast （Ca+Yeast）， and Ca combined with lipopolysaccharide （Ca+LPS）. MethodForty SPF male SD rats were randomly divided into normal group， Ca group， Ca+Yeast group， and Ca+LPS group， with 10 rats in each group. The Ca group， Ca+Yeast group， and Ca+LPS group received an intraperitoneal injection of Ca （10 mg·kg^-1） on the first day. The Ca+LPS group received an intraperitoneal injection of LPS （50 μg·kg^-1） on the second day， and the Ca+Yeast group received a subcutaneous injection of dry yeast suspension （2 mg·kg^-1） on the back on the second day. The rectal temperature of each group was dynamically observed after modeling. After 24 hours of modeling， the macroscopic evaluation indexes， including tongue manifestation， pulse， and black tail length in each group were observed. The PeriCam PSI imaging system was used to detect the blood flow perfusion of the rat tail. The automatic hemorheology analyzer was used to measure the whole blood viscosity and plasma viscosity of each group. The PL platelet function analyzer was used to detect the platelet aggregation rate of the rats. The enzyme-linked immunosorbent assay （ELISA） was used to detect the interleukin-6 （IL-6） level in the rat plasma. The myocardial tissue， brain tissue， and lung tissue of each group of rats were observed by hematoxylin-eosin （HE） staining. ResultCompared with the normal group， all three model groups showed varying degrees of black tail （P<0.05， P<0.01）， reduced blood flow perfusion at the tail end （P<0.05， P<0.01）， decreased R， G， and B values of tongue manifestation （P<0.05， P<0.01）， and increased maximum platelet aggregation rate （P<0.05， P<0.01）. The pulse amplitudes of the Ca+Yeast group and the Ca+LPS group were lower than that of the normal group （P<0.05， P<0.01）. In addition， the average rectal temperature of the Ca+Yeast group increased after 24 hours of modeling （P<0.01）， and the low-， medium-， and high-shear whole blood viscosity and plasma viscosity increased （P<0.05， P<0.01） as compared with those in the normal group. Additionally， the expression level of the plasma inflammatory factor IL-6 was significantly up-regulated （P<0.05）. Pathological morphology results showed that the Ca+Yeast group had the most severe pathological changes， with small foci of myocardial fiber dissolution， inflammatory cell infiltration， and fibroblast proliferation observed. In the hippocampal area， the neurons were sparse and had undergone red degeneration. In the small focus of the lung interstitium， lymphocytes and neutrophils were infiltrated. ConclusionThe animal model of combined stasis and toxin syndrome was properly established using Ca+Yeast. The systematic evaluation system of the model， which includes traditional Chinese medicine four diagnostic information， western medicine microscopic indicators， and tissue pathological morphology， is worthy of consideration and reference by researchers.

OBJECTIVE To investigate the potential developmental toxicity and delayed toxicity of Fuganline oral liquid(FGLOL)after long-term administration in juvenile SD rats via a three-stage juve-nile animal study(JAS).METHODS Stage 1:according to the proposed clinical dose for infants within one year of age,FGLOL 3.88,11.64,38.75 g·kg-1 was orally administered to rats of postnatal day 4(PND4)rats for 18 days,and the drug was stopped for 3 weeks.Stage 2:according to the proposed clinical dose for children ages 1 to 6,FGLOL 3.88,11.64,38.75 g·kg-1 was orally administered to PND15 rats for 31 d,and the drug was discontinued for 3 weeks.Stage 3:according to the proposed clinical dose for children aged 7 to 12,FGLOL 29.06,58.13,116.25 g·kg-1 was orally administered to PND40 rats for 66 d,and the drug was stopped for 4 weeks.The effects of FGLOL on health status,food intake,body mass,growth and development,nerve reflex development,learning and memory ability,physical development(body length),bone development(bone mineral density),hematology and coagulation(white blood cells,red blood cells and platelet count),blood biochemistry(glutamate dehydrogenase,urea nitrogen and triglycerides)and histopathology were investigated in young rats.RESULTS In the three-stage JAS test,long-term administration of FGLOL did not cause rat death,and no toxicological effects were observed on body mass,growth and development,nerve reflex development,physical development,bone development,hematology and coagulation,blood biochemistry and histopathology of juvenile rats compared with the vehicle control group.CONCLUSION The no observed adverse effect level(NOAEL)of FGLOL is 38.75 g·kg-1 for the JAS test corresponding to humans between 1 and 6 years old,while the NOAEL of FGLOL is 116.25 g·kg-1 for the JAS test and repeated drug toxicity test corresponding to humans aged 7 to 12.

OBJECTIVE To investigate the effects of Qinxiang Qingjie oral liquid(QXQJ)on growth and development after repeated administration of 18 d to postnatal day 4(PND4)rats.METHODS The number and sex of PND2 pups were adjusted using the cross-breeding method.These pups were ran-domly divided into the normal control,QXQJ 3.45,10.35 and 28.05 g·kg-1 groups.PND4,juvenile rats were ig given QXQJ every day,while the normal control group was given pure water,once a day,for 18 d,before observation of 3 weeks was resumed.During the experiment,the general condition,body mass,growth and development,physique,bone,hematology and coagulation of the rats in each group were detected.RESULTS 18 d after continuous administration of QXQJ,there was no obvious effect on the food intake,growth and development,nerve reflex,spontaneous behavior,hematology,coagula-tion,blood biochemistry,immunity,growth hormone,histopathology and other examination indexes of juve-nile rats.From PND5,juvenile rats in the QXQJ 10.35 and 28.05 g·kg-1groups developed yellow-brown soft or loose stools and abdominal distention,but the symptoms generally recovered at PND22.The body mass,top-rump length,tail length and limb length of the juvenile rats in the 28.05 g·kg-1 group were signifi-cantly lower at PND7(P<0.05),but recovered one week after drug withdrawal.The bone mineral specific gravity and bone mineral density of the 28.05 g·kg-1 group were significantly lower than those of the normal control group at PND22(P<0.05),but there was no significant difference at PND42.CONCLU-SION QXQJ can cause such indigestion symptoms as yellow brown soft stool or loose stool and abdominal enlargement in unweaned juvenile rats,thus affecting the physical development indicators of rats,but the symptoms can recover after withdrawal of medication or withdrawal from milk.The no observed adverse effect level(NOAEL)of QXQJ administered to 4-day-old rats for 18 d is 3.45 g·kg-1.