Objective: To investigate the feasibility and accuracy of sentinel lymph node biopsy(SLN) following neoadjuvant chemotherapy.Methods:Sentinel lymph node biopsy was evaluated following two or three cycles of neoadjuvant chemotherapy with pharmorubicin /cyclophosphamide/5-FU(CEF,48 patients) or pharmorubicin /cyclophosphamide / taxotere(CET,12 patients).Two ml 1% methylene blue was subcutaneously injected at 4 sites of the skin over the tumor before radical operation.Pathohistological results were assessed for all the specimen including blue lymph node and other axillary lymph node(ALND). Results:Among the 66 patients SLN was identified in 60 of them(90%).Residual metastatic disease was identified in 23 cases on SLN,including 15 positive and 8 negative node on ALND,37 cases were completely negative on SLN including 35 negative and 2 positive node on ALND,and SLN was falsely negative in 2 cases(8%).Conclusion:The success rate of sentinel node identification and the predict ability of the SLN for the pathologic status of the adjacent non-SLNs do not seem to be altered after neoadjuvant therapy.

Muramidase-released protein(MRP)is now being recognized as a critical indicator of the virulence and pathogenicity of Streptococcus suis(S.suis).However,the identification of viable therapeutics for S.suis infection was hindered by the absence of an explicit mechanism for MRP-actuated inflammation.Dihydroartemisinin(DhA)is an artemisinin derivative with potential anti-inflammatory activity.The modulatory effect of DhA on the inflammatory response mediated by the virulence factor MRP remains obscure.This research aimed to identify the signaling mechanism by which MRP triggers the innate immune response in mouse spleen and cultured macrophages.With the candidate mechanism in mind,we investigated DhA for its ability to dampen the pro-inflammatory response induced by MRP.The innate immune response in mice was drastically triggered by MRP,manifesting as splenic and systemic inflammation with splenomegaly,immune cell infiltration,and an elevation in pro-inflammatory cyto-kines.A crucial role for Toll-like receptor 4(TLR4)in coordinating the MRP-mediated inflammatory response via nuclear factor-kappa B(NF-κB)activation was revealed by TLR4 blockade.In addition,NF-KB-dependent transducer and activator of transcription 3(STAT3)and mitogen-activated protein kinases(MAPKs)activation was required for the inflammatory signal transduction engendered by MRP.Intriguingly,we observed an alleviation effect of DhA on the MRP-induced immune response,which referred to the suppression of TLR4-mediated actuation of NF-KB-STAT3/MAPK cascades.The inflam-matory response elicited by MRP is relevant toTLR4-dependent NF-κB activation,followed by an increase in the activity of STAT3 or MAPKs.DhA mitigates the inflammation process induced by MRP via blocking the TLR4 cascade,highlighting the therapeutic potential of DhA in targeting S.suis infection diseases.

To identify acute renal allograft rejection biomarkers in human serum, two-dimensional differential in-gel electrophoresis (2-D DIGE) and reversed phase high-performance liquid chromatography (RP-HPLC) followed by electrospray ionization mass spectrometry (ESI-MS) were used. Serum samples from renal allograft patients and normal volunteers were divided into three groups: acute rejection (AR), stable renal function (SRF) and normal volunteer (N). Serum samples were firstly processed using Multiple Affinity Removal Column to selectively remove the highest abundance proteins. Differentially expressed proteins were analyzed using 2-D DIGE. These differential protein spots were excised, digested by trypsin, and identified by RP-HPLC-ESI/MS. Twenty-two differentially expressed proteins were identified in serum from AR group. These proteins included complement C9 precursor, apolipoprotein A-IV precursor, vitamin D-binding protein precursor, beta-2-glycoprotein 1 precursor, etc. Vitamin D-binding protein, one of these proteins, was confirmed by ELISA in the independent set of serum samples. In conclusion, the differentially expressed proteins as serum biomarker candidates may provide the basis of acute rejection noninvasive diagnosis. Confirmed vitamin D-binding protein may be one of serum biomarkers of acute rejection. Furthermore, it may provide great insights into understanding the mechanisms and potential treatment strategy of acute rejection.

Objective:To analyze the tendency of incidence and mortality of mechanical injuries among Chinese residents from 1990 through 2019 and to estimate the age-period-cohort effect.Methods:Based on the Global Burden of Disease (GBD) 2019 database, the incidence and mortality data of mechanical injuries among Chinese residents from 1990 to 2019 were extracted. The trends of age-standardized incidence rate (ASIR) and age-standardized death rate (ASDR) of mechanical injuries among Chinese residents by gender was analyzed using the joinpoint regression model, and the annual percent change (APC) and average annual percent change (AAPC) were calculated. The age-period-cohort model was used to quantitatively assess the effects of age, period, and cohort on ASIR and ASDR for mechanical injuries.Results:① Overall tendency: from 1990 to 2019, the ASIR of mechanical injuries showed an increasing trend (540.95/100 000 in 1990 vs. 815.34/100 000 in 2019), and the ASDR first increased slightly and then decreased (2.62/100 000 in 1990 vs. 2.87/100 000 in 2005 vs. 1.77/100 000 in 2019) among Chinese residents. During the observation period, ASIR and ASDR for mechanical injuries of male were higher than female. ② Joinpoint regression model analysis showed that the ASIR of mechanical injuries had a fluctuating trend of increasing first and then decreasing and then rising rapidly among Chinese residents from 1990 to 2019 (AAPC = 1.42%, t = 9.59, P < 0.001). The ASIR of the Chinese male showed a slight decrease and then continued to increase (AAPC = 1.47%, t = 8.72, P < 0.001), while the ASIR of the Chinese female showed a rapid rising at first, then rapidly declining and then rising again (AAPC = 1.31%, t = 12.11, P < 0.001). From 1990 to 2019, the ASDR of mechanical injuries showed a fluctuating downward trend of first decreasing, then increasing, and then rapidly decreasing among Chinese residents (AAPC = -1.39%, t = -6.72, P < 0.001). The decrease rate of ASDR among male was as same as that among all population (AAPC = -1.44%, t = -7.29, P < 0.001), but the decrease rate of ASDR in female was relatively slow (AAPC = -1.08%, t = -4.54, P < 0.001). ③ Age-period-cohort model analysis showed that, with the increase of age, the risk of mechanical injuries among the overall population, male and female in China increased, then decreased, and then increased rapidly. The first small peak was at the age of 45-49 years old in male and 65-69 years old in female. The overall death risk showed an increasing trend with age, with a slowly increasing trend before 75 years old, and a sudden increase after 75 years old. The peak age of death risk was between 90 and 94 years. In terms of period effect, the risk of mechanical injuries showed a gradually increasing trend with time among the overall population, male, and female in China, and the risk of death showed a trend of decreasing first and then rapidly increasing and then decreasing. In terms of cohort effect, the risk of mechanical injuries among the overall population, male, and female in China showed a gradual upward trend with the increase in the birth year, and the risk of death showed an M-shaped trend. Conclusions:From 1990 to 2019, the incidence of mechanical injuries showed an increasing trend, and the mortality increased first and then decreased. Although the disease burden has improved, it is still high. More attention needs to be paid to the prevention and control of mechanical injuries, especially in the young population.

Objective To evaluate the surgical strategy for pulmonary valve preservation in repair of tetralogy of Fallot (TOF) and analyze the outcomes in young children patients.Methods A total of 211 TOF younger children less than threeyear-old between January 2009 and December 2015 had received pulmonary valve-sparing(PVS) surgical repair.At the end of the procedure,the peak RV/LV pressure ratio(PRV/PLV) and transannular pressure gradient were performed in all patients.114 patients had higher PRV/PLV rati ≥ 0.8.The former 54 patients,right ventricle infundubulum sparing (RVIS) stragery were made to relieve the RVOTO.However,only 8 patinets of the later 60 cases had received RVIS in TOF repair,whose systemic blood pressure was instable with the large dose of dopamine≥10 μg · kg-1 · min-1 and epinephrine≥0.05 μg · kg-1 · min-1 or the transannular pressure gradient≥30 mmHg (1 mmHg =0.133 kPa).114 patients were divided by two group(52 cases in PVS group and 62 cases in RVIS group) and compared by the early outcomes.Results The median cardiopulmonary bypass time of RVIS group was significantly more than that of PVS group[(110.3 ± 12.0)min vs(77.7 ± 10.0)min].The postoperative index of the patients in PVS group,including transannular pressure gradient [(21.0 ± 5.4) mmHg vs (16.0 ± 3.6) mmHg,P ＜ 0.05],PRV/PLV ratio(0.82 ± 0.03 vs.0.67 ± 0.12,P ＜ 0.01),median using time of dopamine and epinephrine[(6.03 ±9.60)days vs.(4.20 ±1.90)days,P＜0.01],median extubation time[(81.2 ±27.6)h vs.(38.5 ±33.0) h,P ＜ 0.01],ICU stay time [(6.3 ± 1.7) days vs.(4.3 ± 1.9) days,P ＜ 0.01],using of peritoneal dialysis (8/52 vs 4/62,P ＜ 0.01)were more than those in RVIS group.There was no difference of mortality between two groups.Fellow up 12-50 months,there was no difference of LVEF,MPI and TAPSE between two groups.However,the severity of pulmonary regurgitation in patients of PVS group was significant less than those of RVIS group.Conclusion PVS and RVIS in TOF repair could decrease the severity of pulmonary regurgitation after operation.

Deregulation of endothelial nitric oxide synthase (eNOS) plays an important role in the development of multiple cardiovascular diseases. Our recent study demonstrated that genistein supplementation attenuates pulmonary arterial hypertension in broilers by restoration of endothelial function. In this study, we investigated the molecular mechanism by using broiler pulmonary arterial endothelial cells (PAECs). Our results showed that genistein stimulated a rapid phosphorylation of eNOS at Ser(1179) which was associated with activation of eNOS/NO axis. Further study indicated that the activation of eNOS was not mediated through estrogen receptors or tyrosine kinase inhibition, but via a phosphatidylinositol 3-kinase (PI3K)/Akt-dependent signaling pathway, as the eNOS activity and related NO release were largely abolished by pharmacological inhibitors of PI3K or Akt. Thus, our findings revealed a critical function of Akt in mediating genistein-stimulated eNOS activity in PAECs, partially accounting for the beneficial effects of genistein on the development of cardiovascular diseases observed in animal models.
Animals ; Cell Line ; Chickens ; Disease Models, Animal ; Endothelium, Vascular/drug effects/*metabolism/pathology ; Enzyme Activation/drug effects ; Female ; Genistein/*pharmacology ; Humans ; Hypertension, Pulmonary/drug therapy/*metabolism/pathology ; Nitric Oxide Synthase Type III/genetics/*metabolism ; Oncogene Protein v-akt/*metabolism ; Phosphorylation ; Signal Transduction/drug effects

Objective: To investigate the prevalence and risk factors of neck and shoulder pain (NSP) among automobile manufacturing workers and to provide a theoretical basis for prevention of NSP. Methods: From November 5 to November 19, 2017, a total 446 works who had worked for more than one year were recruited from an automobile plant by cluster sampling method. Chi square test and unconditional logistic regression were used to exam the relation between influencing factors and NSP. Results: The annual prevalence rate of NSP was 34.8%. Multifactor regression analysis showed that age、work fatigue、department staff shortages、lifting heavy objects in awkward positions、neck flexion foreword and prolong sitting position work were the risk factors of NSP (OR=2.18, 95%CI:1.49~3.18; OR=4.52, 95%CI:1.27~16.00; OR=1.66, 95%CI:1.04~26.68; OR=2.10, 95%CI:1.16~3.81; OR=2.25, 95%CI:1.39~3.66; OR=2.42, 95%CI:1.06~5.56) and work break was the benefit factors of NSP (OR=0.58, 95%CI:0.36~0.94) . Conclusion The annual prevalence rate of NSP among automobile manufacturing workers was high. Lifing heavy objects、awkward working positions and unreasonable work arrangement were the major risk factors of NSP, and work break can effectively reduce the risk of NSP. Effective ergonomic intervention should be carried out to prevent the occurrence of NSP.

Objective:To explore the core competency of doctors in tertiary public hospitals in regions of different income levels in China, and provide reference for promoting such competency and related policy formulation.Methods:Using multi-stage stratified cluster sampling method, 195 tertiary public hospitals in 16 provinces of China were selected from November 2021 to March 2022. 200 doctors were sampled from each hospital. A self-designed questionnaire was used to investigate the status of doctors′ core competencies, as well as the status of their postgraduate medical education and continuing medical education. According to the per capita gross regional product of each province in China Statistical Yearbook 2022, each province was divided into high, middle and low income regions, and the questionnaire data were descriptively analyzed, while χ2 test was used to compare the differences between groups. Results:A total of 32 673 valid questionnaires were collected. There were 12 135 doctors (37.14%) in China who had received comprehensive education and training of core competency in all dimensions. Among the dimensions of self-rated core competency of the surveyed doctors, there were 10 019 doctors (30.66%) with insufficient teaching ability and 438 (1.34%) with insufficient professional quality, and there was no significant difference between regions ( P>0.05). There were 2 385 (27.08%), 2 528 (27.55%) and 3 646 (24.82%) doctors in high-, middle- and low-income regions with insufficient lifelong learning ability, respectively. The proportion of doctors in middle- and high-income regions was higher than that in low-income ones ( P<0.05). There were 1 317 (15.57%), 1 290 (14.06%) and 2 719 (18.51%) doctors with insufficient knowledge and skills in high-, middle- and low-income areas, respectively. The proportion of doctors in low-income regions was higher than that in middle- and high-income regions ( P<0.05). The proportion of doctors who did not receive any kind of postgraduate medical education or continuing medical education in low-income regions was 7.33% (1 077 people), higher than that in high-income and middle- income ones ( P<0.05); 50.44% (4 442 people) of surveyed doctors in high-income regions believed that for standardized training of resident physicians (hereinafter referred to as residential training), the clinical teachers were " overworked to take this job", which was higher than that in middle- and low-income regions ( P<0.001); In middle-income regions, 46.16% (4 235 people) and 43.46% (3 987 people) believed that the salary residents and specialized physicians in standardized training (hereinafter referred to as specialized training) was too low, while 42.47% (3 897 people) and 30.44% (2 793 people) believed that the clinical practice opportunities of students were limited, both of which were higher than those in high-income and low-income regions ( P<0.001); 34.91% (5 128 people) of surveyed doctors in low-income regions believed that the investment was insufficient for training bases of residential training, 27.81% (4 085 people) of those held that training bases for specialized training were unevenly distributed, and 33.19% (4 876 people) of those held that continuing medical education was plagued by " insufficient promotion coverage, and insufficient opportunities for primary doctors", all of which being higher than those in high- and middle-income regions ( P<0.001). Conclusions:There is an obvious need to improve the core competence of doctors in the teaching ability dimension of tertiary public hospitals in China, especially in middle- and high-income regions for lifelong learning, and in low-income regions for knowledge and skills; There are differences between postgraduate medical education and continuing medical education systems in regions of different income levels in China. It is necessary to improve the competency oriented postgraduate medical education and continuing medical education systems.

Objective To determine the effect of isopsoralen(ISO)on the healing of tibia fracture in mice and explore its underlying mechanism.Methods Fifty male C57BL/6 mice(2 month old,20±2 g)were randomly divided into model group and ISO treatment group,with 25 animals in each group.From the 3rd day after modeling,the mice from the ISO group were given an intragastric gavage of 40 mg/kg ISO,once per day for 28 consecutive days,while those of the model group was given same volume of normal saline in same way.On the 7th,14th,21st,and 28th day after gavage,the tibia on the surgical side was taken,and the fracture area was quantified by bone volume/total volume(BV/TV)after micro-CT scanning.The healing and shaping of the fracture end were observed through HE staining.ELISA was used to detect the serum contents of bone alkaline phosphatase(BALP)and procollagen type I N-terminal peptide(PINP)on the 14th day of gavage.Western blotting was employed to determine the expression levels of Collagen Ⅰ,Runx2,BMP2,OSX,and VEGF in the tibial callus tissue in 7 and 14 d after gavage.Vascular perfusion was applied to observe the callus microvessels in 28 d to quantitatively analyze the vascular volume fraction and vessel diameter.Immunohistochemical staining was conducted to observe the expression of VEGF in the callus in 14 d after gavage.Results HE staining displayed that the ISO group had faster healing process than the model group.Micro-CT quantification results showed that the ISO group had higher BV/TV ratio in 7 d after gavage though no statistical difference,significantly higher ratio in 14 d(P＜0.05),but obviously lower ratio in 21 and 28 d after gavage(both P＜0.05)when compared with the model group.The serum contents of BALP and PINP were also remarkably higher in the ISO group than the model group(P＜0.05).Western blotting results indicated that the expression levels of Collagen Ⅰ,Runx2,BMP2,OSX and VEGF in the ISO group were higher than those in the model group(P＜0.05).The results of angiography revealed that the vascular volume fraction and vessel diameter were notably increased in the ISO group than the model group(both P＜0.05).Immunohistochemical assay showed that the expression of VEGF was higher in the ISO group than the model group(P＜0.05).Conclusion ISO can improve the activity of osteoblasts,increase the expression of osteogenesis-related proteins,and accelerate the angiogenesis to promote fracture healing.

To identify acute renal allograft rejection biomarkers in human serum, two-dimensional differential in-gel electrophoresis (2-D DIGE) and reversed phase high-performance liquid chromatog-raphy (RP-HPLC) followed by electrospray ionization mass spectrometry (ESI-MS) were used. Serum samples from renal allograft patients and normal volunteers were divided into three groups: acute rejec-tion (AR), stable renal function (SRF) and normal volunteer (N). Serum samples were firstly processed using Multiple Affinity Removal Column to selectively remove the highest abundance proteins. Differ-entially expressed proteins were analyzed using 2-D DIGE. These differential protein spots were ex-cised, digested by trypsin, and identified by RP-HPLC-ESI/MS. Twenty-two differentially expressed proteins were identified in serum from AR group. These proteins included complement C9 precursor,apolipoprotein A-Ⅳ precursor, vitamin D-binding protein precursor, beta-2-glycoprotein 1 precursor,etc. Vitamin D-binding protein, one of these proteins, was confirmed by ELISA in the independent set of serum samples. In conclusion, the differentially expressed proteins as serum biomarker candidates may provide the basis of acute rejection noninvasive diagnosis. Confirmed vitamin D-binding protein may be one of serum biomarkers of acute rejection. Furthermore, it may provide great insights into un-derstanding the mechanisms and potential treatment strategy of acute rejection.