ObjectiveTo investigate the features of serum HBV RNA in different stages of the natural history of chronic hepatitis B virus （HBV） infection without antiviral treatment， as well as its correlation with serum HBV DNA and HBsAg. MethodsA total of 306 treatment-naïve patients with chronic HBV infection who attended Department of Infections Diseases and Hepatoloty， the Second Hospital of Shandong University from January 2023 to June 2024 were divided into six groups based on the different stages of natural history， i.e.， HBeAg-positive chronic HBV infection group with 29 patients， HBeAg-positive chronic hepatitis B （CHB） group with 107 patients， HBeAg-negative chronic HBV infection group with 18 patients， HBeAg-negative CHB group with 60 patients， HBeAg-positive indeterminate-phase chronic HBV infection group with 7 patients， and HBeAg-negative indeterminate-phase chronic HBV infection group with 85 patients. Real-time isothermal RNA amplification was used to measure serum high-sensitivity HBV RNA. The Kruskal-Wallis H test was used for comparison between multiple groups of continuous data， while the Mann-Whitney U test was used for comparison between two groups. The Spearman method was used to investigate the correlation of HBV RNA with HBV DNA and HBsAg. ResultsThe HBeAg-positive chronic HBV infection group showed the highest level of serum HBV RNA ［7.5 （7.4‍ ‍—‍ ‍7.9） log₁₀ copies/mL］， followed by the HBeAg-positive CHB group ［7.4 （6.4‍ ‍—‍ ‍7.9） log₁₀ copies/mL］， the HBeAg-negative CHB group ［4.5 （3.0‍ ‍—‍ ‍5.7） log₁₀ copies/mL］， and the HBeAg-negative chronic HBV infection group ［1.0 （1.0‍ ‍—‍ ‍2.0） log₁₀ copies/mL］； the HBeAg-positive indeterminate-phase chronic HBV infection group had a serum HBV RNA level of 3.9 （3.7‍ ‍—‍ ‍5.7） log₁₀ copies/mL， and the HBeAg-negative indeterminate-phase chronic HBV infection group had a serum HBV RNA level of 2.0 （1.0‍ ‍—‍ ‍3.0） log₁₀ copies/mL； there was a significant difference in serum HBV RNA level between the six groups （H=830.770， P<0.001）. There was a significant difference in HBV RNA level between the HBeAg-positive chronic HBV infection group and all the other groups except the HBeAg-positive CHB group （all P<0.001）. In the 306 patients with HBV infection， HBV RNA was strongly correlated with HBV DNA （r=0.92， P<0.001） and was moderately correlated with HBsAg （r=0.67， P<0.001）. The correlation between serum HBV RNA and HBsAg in HBeAg-positive patients （r=0.61， P<0.001） was stronger than that in HBeAg-negative patients （r=0.31， P<0.001）. For the patients with HBeAg-positive chronic HBV infection， the male patients with ALT>30 U/L and the female patients with ALT>19 U/L had a significantly lower serum HBV RNA level than the male patients with ALT≤30 U/L and the female patients with ALT≤19 U/L （P<0.001）， and there was no significant difference in serum HBV RNA level between the latter group of patients and the HBeAg-positive CHB group （P>0.05）. ConclusionIn patients with chronic HBV infection who do not receive antiviral therapy， there is a difference in serum HBV RNA level in different stages of natural history， and serum HBV RNA level has the strongest correlation with HBV DNA and a relatively weak correlation with HBsAg. In patients with HBeAg-positive chronic HBV infection， serum HBV RNA level in male patients with ALT>30 U/L and female patients with ALT>19 U/L are in the transition stage between HBeAg-positive chronic HBV infection and HBeAg-positive CHB.

Objective To analyze the predictive value of serum levels of procalcitonin(PCT)and cytokines on the prognosis of patients with COVID-19 at admission.Methods From November 2022 to February 2023,patients diagnosed with COVID-19 who were admitted to Beijing Chest Hospital were enrolled.Chemiluminescence was used to detect serum PCT levels,and flow microsphere array was used to detect serum cytokines IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17A,IL-17F,IL-22,TNF-α,TNF-β,IFN-γ level.ICU admission,mechanical ventilation and in-hospital death were defined as poor prognosis.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.Results A total of 176 patients with complete data were included,including 134 in the PCT-normal group and 42 in the PCT-elevated group,with a median age of 71.50 years and 71.59%males.Patients in the PCT elevated-group had significantly higher rates of ICU admission(38.41%vs.13.11%,P<0.05),mechanical ventilation(76.92%vs.24.59%,P<0.001)and in-hospital mortality(38.46%vs.6.56%,P<0.001)were significantly higher than those in the PCT-normal group.Serum levels of cytokines IL-6(7.40 pg/mL vs.4.78 pg/mL,P = 0.033 4)and IL-8(10.97 pg/mL vs.5.92 pg/mL,P<0.001)were significantly higher in patients with poor prognosis than in those with good prognosis.The area under the curve for PCT,IL-6,and IL-8 to predict poor prognosis in COVID-19 patients was 0.687,0.660,and 0.746,respectively;sensitivity was 52.78%,55.17%,and 72.41%,respectively;and specificity was 81.58%,74.19%,and 74.19%,respectively,as calculated from the ROC curve.When PCT,IL-6 and IL-8 jointly predict the prognosis of COVID-19 patients,the area under the curve is 0.764,the sensitivity is 70.00%,and the specificity is 80.00%.Conclusion Serum PCT and cytokines IL-6 and IL-8 could be used as predictive markers for poor prognosis in patients with COVID-19.

BACKGROUND:Bone defects are caused by many factors,such as inflammation,tumor,trauma or bone diseases.Erythropoietin can promote the differentiation of mesenchymal stem cells into osteoblasts and osteoclasts and act on vascular endothelial cells to induce angiogenesis and accelerate the repair of bone and cartilage defects.Erythropoietin is a growth factor with potential application in bone tissue engineering construction. OBJECTIVE:To expound the application and potential mechanism of erythropoietin in bone tissue engineering. METHODS:The first author searched the related articles published in CNKI,WanFang,VIP,and PubMed databases from 2004 to 2022 by computer.Search terms were"erythropoietin,bone defect,bone regeneration,angiogenesis,osteogenesis,osteoblast,osteoclast,bone tissue engineering"in Chinese and English.Finally,64 articles were included for review. RESULTS AND CONCLUSION:(1)Erythropoietin can directly act on osteoblasts and osteoclasts in the bone marrow microenvironment by promoting the differentiation of mesenchymal stem cells into osteoblasts,osteoclasts,adipocytes,nerve cells and stromal cells.The activation of Wnt/β-catenin,hypoxia-inducible factor 1α/vascular endothelial growth factor,p38 MAPK and EphrinB2/EphB4 signaling pathways mediates the osteogenic differentiation of mesenchymal stem cells.(2)Erythropoietin can not only regulate the production of erythrocytes to alter the oxygen-carrying capacity of blood but also stimulate vascular endothelial cells to promote angiogenesis.The new blood vessels can carry oxygen,nutrients,growth factors,and bone progenitor cells necessary for osteogenesis to the osteogenic site,thereby promoting bone formation and fracture healing.(3)Currently,erythropoietin is being used as a growth factor with osteogenic and angiogenic effects in various types of scaffold materials such as chitosan,polycaprolactone,bioceramics,and nanofibers through various drug delivery methods.Erythropoietin,along with other growth factors such as bone morphogenetic protein-2 and bone morphogenetic protein-9,has been applied to the surface of scaffold materials to participate in the repair of bone defects.Erythropoietin has demonstrated excellent practicality in the construction of new tissue-engineered bone and has potential clinical application value.

Objective To investigate the correlation between the voice handicap index(VHI)and motor symp-toms,cognitive function,and respiratory function in Parkinson disease(PD).Methods A total of 124 patients with PD hospitalized in the Parkinson Medical Center,Beijing Rehabilitation Hospital,Capital Medical University from April 2020 to March 2023 were included,and the general data of the subjects were collected.We used the Hoehn and Yahr scale to determine the clinical stage of the PD patients;the Movement Disorder Society Unified Parkinson Disease Rating Scale Part Ⅲ(MDS-UPDRS Ⅲ)to assess the motor symptoms of the patients;the VHI-10 to assess voice status;the Parkinson's Disease-Cognitive Rating Scale(PD-CRS),the Trail Making Test(TMT),and the Digit Symbol Substitution Test(DSST)to assess cognitive function;and the forced vital capacity(FVC),forced expiratory volume in the 1st second(FEV1),FEV1/FVC,and maximal voluntary ventilation(MVV)to measure respiratory function.The correlation between voice sta-tus and motor symptoms,cognitive function,and respiratory function in patients with PD using Spearman correlation analy-sis.Results The VHI-10 score of the PD patients was positively correlated with the MDS-UPDRS Ⅲ score,facial expression score,rigidity score,axial symptom score,and time to complete the TMT(r=0.20,0.22,0.18,0.31,0.22;P＜0.05),and was negatively correlated with the DSST score and FEV1/FVC(r=-0.24,-0.24;P＜0.05).Conclusion Voice impairment in PD patients may be influenced by multiple factors and may correlate with motor symptoms,cognitive function,and respira-tory function.

The purpose of this study was to investigate the damage mechanism of pathogenic E.coli on mouse brain microvascular endothelial cells(BMEC cells)and mouse alveolar macrophages(MH-S cells),as well as the lung and brain of healthy mice.In this study,BMEC cells and MH-S cells were infected with pathogenic E.coli strains,and cell morphological changes were observed.Plate counting method was used to detect the adhesion and invasion ability of the strains to cells and the number of bacteria in the lungs and brains of mice.RT-qPCR was used to detect the ex-pression of TNF-α,IL-1β and IL-6 genes in cells and mouse organs at different time periods.West-ern blot was used to detect the expression of p-NF-κB,p-JAK2 and p-STAT3 proteins related to inflammation in cells and mouse organs after infection.The results showed that the cell culture medium of the infection group was turbid,the cell vision became dark and blurred,some cells shrank and died,and more fragments were produced.The adhesion rate and invasion rate of BMEC cells at 3 h were significantly lower than those at 6 h(P＜0.050),and the adhesion rate and inva-sion rate of MH-S cells at 3 h were significantly higher than those at 6 h(P＜0.010).Infected mice had a large area of swelling and bleeding in the brain,and the lungs had different degrees of swell-ing and bleeding.The bacterial load in the brain and lung was the highest at 12 h.Compared with the control group,the mRNA expression levels of IL-1β,IL-6 and TNF-α in the infection group were significantly increased at 3 h and 6 h(P＜0.050),and the mRNA expression levels of inflam-matory factors in BMEC cells and MH-S cells were the highest at 6 and 3 h,respectively.The mR-NA expression of inflammatory factors in the brain and lung of infected mice showed a trend of in-creasing first and then decreasing with time,with the highest expression at 12 h after infection.The expression levels of p-NF-κB protein in BMEC cells,MH-S cells,lung and brain tissues of mice in the infection group were significantly higher than those in the control group(P＜0.001),and the expression levels of p-JAK2 protein and p-STAT3 protein were significantly lower than those in the control group(P＜0.050).The above results showed that pathogenic E.coli could adhere and invade BMEC cells and MH-S cells,colonize in lung and brain tissues of mice,promote the expres-sion of NF-κB protein in cells and tissues,inhibit the expression of JAK2 protein and STAT3 pro-tein,and then stimulate cells and tissues to produce inflammatory response.

BACKGROUND: Lung cancer is still the malignant tumor with the highest morbidity and mortality in China. Lung adenocarcinoma is the most common subtype, and the number of lung cancer presenting as mixed ground glass nodule (mGGN) in imaging is gradually increasing. Visceral pleural invasion (VPI) is an important factor affecting the prognosis of mGGN type lung adenocarcinoma. The aim of the study is to explore and analyze the risk factors for VPI in mGGN type lung adenocarcinoma. METHODS: From November 2016 to November 2019, 128 patients with mGGN lung adenocarcinoma underwent radical surgical resection in the First Affiliated Hospital of Nanjing Medical University. Their clinical data, including imaging, pathological and biological features, were collected and analyzed retrospectively. There were 40 males and 88 females, aged 60.3±9.3 years ranging from 30 to 81 years. Single factor Chi-square test and multivariate Logistic regression were used to analyze the risk factors of VPI in mGGN type lung adenocarcinoma. RESULTS: Among 128 mGGN patients who met the inclusion criteria, 57 cases were pathologically confirmed with pleural invasion. Between the VPI (+) and VPI (-) group (P<0.05), there were significant differences in gender, maximum diameter of solid component, consolidation tumor ratio (CTR), spicule sign, history of lung disease, family history of hypertension, relation of lesion to pleura (RLP), coursing relationship between bronchi and nodules. In multivariate Logistic regression analysis, RLP (OR=3.529, 95%CI: 1.430-8.713, P=0.006) and coursing relationship between bronchi and nodules (OR=3.993, 95%CI: 1.517-10.51, P=0.005) were found to be independent risk factors for VPI (P<0.05). CONCLUSIONS The possibility of VPI in m GGN lung adenocarcinoma should be evaluated by combining these parameters in clinical diagnosis and treatment. As independent risk factors, RLP and coursing relationship between bronchi and nodules are instructive to identify VPI in mGGN type lung adenocarcinoma.
Adenocarcinoma of Lung/pathology* ; Female ; Humans ; Lung Neoplasms/surgery* ; Male ; Neoplasm Invasiveness ; Pleura/pathology* ; Retrospective Studies ; Risk Factors

The pharmacy of Y anqing Winter （Paralympic）Olympic Village Polyclinic of 2022 Beijing Winter （Paralympic） Olympic Games will be comprehensively managed from five aspects of man ，machine，material，method and environment by adopting the 4M1E management method of quality management tool . In terms of man ，constantly enhanced training and daily health monitoring have been insisted ；in terms of machine ，drug information entry and drug information management have been improved and maintained ；in terms of drugs ，on the basis of drug management ，the management of drugs banned by the World Anti -Doping Agency，class Ⅱ psychotropic drugs and narcotic drugs have been strengthened ；in terms of regulations and environment ，strict pharmacy workflow and management system have been established ，and epidemic prevention closed -loop management requirements have been strictly implemented . From the pre -opening of Yanqing Winter （Paralympic）Olympic Village on January 23，2022 to the official closing of the Village on March 16，2022，the clinic pharmacy dispensed a total of 156 prescriptions（105 prescriptions during the Winter Olympic Games ，51 prescriptions during the Winter Paralympic Games ），including 18 prescriptions from the National （Regional） Olympic Committee and the National （Regional） Paralympic Games team doctors ，2 prescriptions containing stimulants that do not need to be exempted from treatment，1 prescription for narcotics ，and 37 prescriptions for athletes（23.7%）. Ibuprofen tablets ，Diclofenac diethylamine emulsion，Loratadine tablets and other drugs are widely used . The application of 4M1E management method enables the clinic pharmacy to provide perfect and high -quality pharmaceutical services for large -scale events while doing well in epidemic prevention and control .

Platelets buoy up cancer metastasis via arresting cancer cells, enhancing their adhesion, and facilitating their extravasation through the vasculature. When deprived of intracellular and granular contents, platelet decoys could prevent metastatic tumor formation. Inspired by these, we developed nanoplatesomes by fusing platelet membranes with lipid membranes (P-Lipo) to restrain metastatic tumor formation more efficiently. It was shown nanoplateletsomes bound with circulating tumor cells (CTC) efficiently, interfered with CTC arrest by vessel endothelial cells, CTC extravasation through endothelial layers, and epithelial-mesenchymal transition of tumor cells as nanodecoys. More importantly, in the mouse breast tumor metastasis model, nanoplateletsomes could decrease CTC survival in the blood and counteract metastatic tumor growth efficiently by inhibiting the inflammation and suppressing CTC escape. Therefore, nanoplatelesomes might usher in a new avenue to suppress lung metastasis.

OBJECTIVE：To evaluate th e effectiveness ，safety and economy of albu min-bound paclitaxel （nab-PTX）in the treatment of breast cancer by using rapid health technology assessment （HTA），and to provide evidence-based reference for drug selection. METHODS ：Retrieved from PubMed ，the Cochrane Library ，CNKI，Wangfang database and other databases ，systematic evaluation/Meta-analysis，HTA and pharmacoeconomic studies about nab-PTX in the treatment of breast cancer were included ；the conclusions were classified and analyzed by using descriptive analysis. RESULTS ：A total of 5 systematic reviews/Meta-analysis ， 8 pharmacoeconomic studies were included in this study. Compared with conventional taxanes ，nab-PTX increased pathological complete response （pCR）rate [OR ＝1.39，95％CI（1.16，1.67），P＜0.001] and event-free survival （EFS）[HR＝0.69，95％CI（0.57， 0.85），P＜0.001] in neoadjuvant chemotherapy （NAC）-treated breast cancer patients. However ，there were no significant differences in overall survival （OS），progression-free survival （PFS），objective response rate （ORR）and disease control rate （DCR）in metastatic breast cancer （MBC）patients between 2 groups. In the terms of safety ，nab-PTX increased the incidence of grade 3-4 sensory neuropathy [OR ＝1.89，95％CI（1.36，2.61），P＜0.001] in MBC patients ，and increased the incidence of neutropenia [OR ＝ 1.52，95％CI（1.23，1.88，P＜0.001]，sensory neuropathy [OR ＝ 2.17，95％CI（1.38，3.40），P＜0.001]，rash [OR ＝1.46，95％CI mei1213@163.com （1.18，1.80），P＜0.001] and fatigue [OR ＝1.28，95％CI（1.04， 1.56）， P＝0.02] in NAC -treated breast cancer patients.Pharmacoeconomic studies showed that nab-PTX could improve the quality adjusted lif e years of MBC patients compared with traditional taxanes ，and it was a economical option. CONCLUSIONS：Nab-PTX enhances pCR in NAC-treated breast cancer patients ，but has no significant advantage in the effectiveness of MBC patients ，and increases the occurrence of ADR. Nab-PTX may have a cost-utility advantage over conventional taxanes for MBC.

Objective The three-dimensional (3D) solid model of medulla oblongata-upper cervical spinal cord based on specimen pathological section data was established, and the stress and strain levels of medulla oblongata-upper cervical spinal cord under dentate process compression were obtained by finite element analysis, so as to provide references for clinical research. Methods Mimics was used to process the slice data, so as to establish the point cloud model. SolidWorks was used to locate, edit and optimize the point cloud model, so as to establish the 3D solid model. HyperMesh was used to establish the finite element model and ANSYS was used for finite element analysis. Results The medulla oblongata-upper cervical spinal cord model with clear boundary between gray matter and white matter and white matter fiber bundle was established. The stress and strain levels and stress-strain curves of white matter and gray matter under different compression degrees were obtained. Conclusions Combined with pathological sections of specimens and reverse engineering, the 3D medulla oblongata-upper cervical spinal cord model with clear morphology and structure of gray/white matter can be established. When the medulla oblongata-upper cervical spinal cord is compressed, the stress level of gray matter is lower than that of white matter, and about 20% of compression is the critical state of white matter. When the disease develops beyond the critical state, the biomechanical properties of white matter may fail, resulting in gray matter damage.