Clinicopathological Features and Long-Term Prognostic Role of Human Epidermal Growth Factor Receptor-2 Low Expression in Chinese Patients with Early Breast Cancer:A Single-Institution Study

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC.Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups.Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszelχ^(2)test,P<0.001,Pearson’s R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%.Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Nucleotide excision repair gene polymorphisms and hepatoblastoma susceptibility in Eastern Chinese children:A five-center case-control study

Objective:Nucleotide excision repair(NER)plays a vital role in maintaining genome stability,and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation.This study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han children.Methods:In this five-center case-control study,we enrolled 966 subjects from East China(193 hepatoblastoma patients and 773 healthy controls).The TaqMan method was used to genotype 19 single nucleotide polymorphisms(SNPs)in NER pathway genes,including ERCC1,XPA,XPC,XPD,XPF,and XPG.Then,multivariate logistic regression analysis was performed,and odds ratios(ORs)and 95%confidence intervals(95%CIs)were utilized to assess the strength of associations.Results:Three SNPs were related to hepatoblastoma risk.XPC rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model(adjusted OR=1.49,95%CI=1.07−2.08,P=0.019;adjusted OR=1.66,95%CI=1.12−2.45,P=0.012,respectively).However,XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model(adjusted OR=0.68,95%CI=0.49−0.95;P=0.024).Stratified analysis demonstrated that these significant associations were more prominent in certain subgroups.Moreover,there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci(eQTLs)and splicing quantitative trait loci(sQTLs)analysis.Conclusions:In summary,NER pathway gene polymorphisms(XPC rs2229090,XPD rs3810366,and XPD rs238406)are significantly associated with hepatoblastoma risk,and further research is required to verify these findings.

Integrated Chinese and Western medicine in the treatment of a patient with podocyte infolding glomerulopathy:A case report

BACKGROUND Podocyte infolding glomerulopathy(PIG)is a newly described and rare glomerular disease.To date,only approximately 40 cases have been reported globally.CASE SUMMARY A 26-year-old female patient presented to our hospital with a complaint of intermittent edema of both lower limbs over the past 2 years.The patient was diagnosed with PIG.She was prescribed corticosteroid therapy in other hospitals during the initial stage,to which she had responded poorly and had developed femoral head necrosis.Therefore,we administered immunosuppressants,reninangiotensin system inhibitors,combined with traditional Chinese medicine.The patient was followed for 1 year,during which her clinical condition improved.CONCLUSION Integrated Chinese and Western medicine may be effective for PIG treatment,which requires active intervention to improve prognosis.

Changes with aging in gastric biomarkers levels and in biochemical factors associated with Helicobacter pylori infection in asymptomatic Chinese population

AIM To observe changes in gastric biomarker levels with age and effects of Helicobacter pylori(H. pylori) infection in a healthy population, and explore factors associated with gastric biomarkers.METHODS Three hundred and ninety-five subjects were selected and underwent physical examinations, biochemical tests, and measurement of serum pepsinogen(PG)Ⅰ and Ⅱ, gastrin-17(G-17) and H. pylori antibody levels. Analyses were made by Student's t-test, ANOVA, Pearson's correlation and multiple linear regressions.RESULTS PGII levels were higher in the ≥ 65-years-old age group(P < 0.05) and PGI/PGII were lower in the ≥ 75-years-old age group(P = 0.035) compared to the 35-44-years-old age group. Levels of low-density lipoprotein cholesterol(LDL-C) were higher(P = 0.009) in H. pylori-infected subjects that were male. LDL-C levels were higher in 55-74-years-old age group(P < 0.05) for H. pylori-infected subjects and 45-64-yearsold age group(P < 0.05) for non-infected subjects compared to 35-44-years-old age group. Hp-Ig G level positively correlated with PGⅠ, PGⅡ and G-17(P < 0.001, P < 0.001, P = 0.006), and negatively correlated with PGI/PGII(P < 0.001). Creatinine positively correlated with PGⅠ, PGⅡ and G-17(P < 0.001, P < 0.001, P < 0.001). Fasting blood glucose(FBG) positively correlated with PGⅠ/PGⅡ and G-17(P < 0.001, P = 0.037). Age positively correlated with PGII and G-17(P = 0.005, P = 0.026).CONCLUSION PGII levels increased while PGI/PGII declined with age in a healthy population. H. pylori infection had an effect on raising LDL-C levels to increase the risk of atherosclerosis in males, especially those of elderly age. Age, H. pylori infection, levels of renal function and FBG were associated with levels of pepsinogens and gastrin.

Chinese expert consensus and practice guideline of totally implantable access port for digestive tract carcinomas

Totally implantable access port is a fully implantable drug delivery system that is implanted subcutaneously and can be retained for a long time.Advantages of ports include a simple nursing process,low risk of infection and embolism,and high patient comfort.In order to promote the standardized application of ports in the treatment of digestive tract tumors and reduce port-related complications,the Chinese Research Hospital Association Digestive Tumor Committee,the Chinese Association of Upper Gastrointestinal Surgeons,the Chinese Gastric Cancer Association,and the Gastrointestinal Surgical Group of Chinese Surgical Society Affiliated to Chinese Medical Association have organized multidisciplinary expert discussions at the General Hospital of the People’s Liberation Army and nationwide expert letter reviews and on-site seminars,and formulated an expert consensus of the operation guidelines.

Radiofrequency ablation for hepatic hemangiomas: A consensus from a Chinese panel of experts

Recent studies have shown that radiofrequency(RF) ablation therapy is a safe, feasible, and effective procedure for hepatic hemangiomas, even huge hepatic hemangiomas. RF ablation has the following advantages in the treatment of hepatic hemangiomas: minimal invasiveness, definite efficacy, high safety, fast recovery, relatively simple operation, and wide applicability. It is necessary to formulate a widely accepted consensus among the experts in China who have extensive expertise and experience in the treatment of hepatic hemangiomas using RF ablation, which is important to standardize the application of RF ablation for the management of hepatic hemangiomas, regarding the selection of patients with suitable indications to receive RF ablation treatment, the technical details of the techniques, therapeutic effect evaluations, management of complications, etc. A final consensus by a Chinese panel of experts who have the expertise of using RF ablation to treat hepatic hemangiomas was reached by means of literature review, comprehensive discussion, and draft approval.

Is new American Thyroid Association risk classification for hereditary medullary thyroid carcinoma applicable to Chinese patients? A single-center study

Objective: The American Thyroid Association (ATA) proposed a new risk classification for hereditary medullary thyroid carcinoma (MTC) in 2015. This study aimed to assess whether the new guidelines are suitable for the Chinese population, and reported our experience on prophylactic thyroidectomy. Methods: A total of 73 patients from 22 families were screened as rearranged during transfection (RET) mutation carriers from 2010 to 2016 in Cancer Hospital, Chinese Academy of Medical Science; the medical history for each patient was collected. Based on the initial treatment, we identified the risk factors for poor prognosis by univariate and multivariate logistic regression. Then, 4 RET mutation carriers were enrolled for prophylactic thyroidectomy, and their pathological data and follow-up outcomes were recorded. Results: In univariate and multivariate logistic regression analyses, age at initial surgery and risk classification were significant risk factors for stage III/IV hereditary MTC at initial diagnosis. The likelihood was increased by 11.6% per year of age at initial surgery [95% confidence interval (95% CI), 1.040-1.198; P=0.002). It was 7.888 times more likely to have III/IV stage disease for ATA highest risk patients, compared to ATA moderate risk individuals (95% CI, 1.607-38.717; P=0.003). Postoperative pathological results showed all 4 multiple endocrine neoplasia type 2A (MEN2A) patients had C-cell hyperplasia (CCH); multifocal malignancies were detected in 3 of them. All 4 patients were cured biochemically, and none developed permanent hypoparathyroidism. Conclusions: In Chinese individuals, hereditary MTC aggressiveness is in line with the new ATA risk classification. Germline RET gene mutation carriers should undergo prophylactic thyroidectomy according to basal serum calcitonin levels.

Changes in pulse pressure × heart rate, hs-CRP, and arterial stiffness progression in the Chinese general population: a cohort study involving 3978 employees of the Kailuan Company

Background Pulse wave velocity(PWV) is a marker of arterial stiffness, which represents sub-clinical atherosclerosis. Pulsatile stress and high-sensitivity C-reactive protein(hs-CRP) are associated with arteriosclerosis. However, there is no prospective data confirming whether changes in pulsatile stress and inflammatory markers affect the progression of arterial stiffness. The aim of this study was to investigate the relationships over time between the effects of changes in pulsatile stress and hs-CRP, and arterial stiffness progression during a 2-year follow-up. Methods We performed a longitudinal study involving 3978 participants. All participants underwent a physical examination in 2010–2011 and 2012–2013, during which we measured participants’ hs-CRP levels, brachial–ankle pulse wave velocity(ba PWV), and pulsatile stress. Results Baseline hs-CRP was correlated with ba PWV(r = 0.18, P = 0.000);however the correlation was weaker than that with systolic blood pressure(r = 0.65), pulsatile stress(r = 0.57), and rate-pressure product(r = 0.58). Multiple linear regression analysis demonstrated that changes in pulsatile stress, mean arterial pressure, and low-density lipoprotein-C(LDL-C) were positively correlated with changes in ba PWV, with correlation coefficients of 0.27, 0.25, and 0.07, respectively, but not with changes in hs-CRP. Moreover, each 100-a U increase in pulsatile stress, 1 mm Hg increase in mean blood pressure, and 1 mmol/L increase in LDL-C was associated with a 3 cm/s, 4.78 cm/s, and 17.37 cm/s increase in ba PWV, respectively. Conclusions Pulsatile stress increases are associated with arterial stiffness progression, but that changes in hs-CRP had no effect on arterial stiffness progression. Hs-CRP may simply be a marker of inflammation in arterial stiffness and has no association with arterial stiffness progression.

Chinese expert consensus on diagnosis and treatment of trauma-induced hypercoagulopathy

Trauma-induced coagulopathy(TIC)is caused by post-traumatic tissue injury and manifests as hypercoagulability that leads to thromboembolism or hypocoagulability that leads to uncontrollable massive hemorrhage.Previous studies on TIC have mainly focused on hemorrhagic coagulopathy caused by the hypocoagulable phenotype of TIC,while recent studies have found that trauma-induced hypercoagulopathy can occur in as many as 22.2%–85.1%of trauma patients,in whom it can increase the risk of thrombotic events and mortality by 2-to 4-fold.Therefore,the Chinese People’s Liberation Army Professional Committee of Critical Care Medicine and the Chinese Society of Thrombosis,Hemostasis and Critical Care,Chinese Medicine Education Association jointly formulated this Chinese Expert Consensus comprising 15 recommendations for the definition,pathophysiological mechanism,assessment,prevention,and treatment of trauma-induced hypercoagulopathy.

Chinese consensus on management of tyrosine kinase inhibitor-associated side effects in gastrointestinal stromal tumors

Tyrosine kinase inhibitors(TKIs) have improved the overall survival of patients with gastrointestinal stromal tumors(GISTs), but their side effects can impact dose intensity and, consequently, the clinical benefit. To date, no guideline or consensus has been published on the TKI-associated adverse reactions. Therefore, the Chinese Society of Surgeons for Gastrointestinal Stromal Tumor of the Chinese Medical Doctor Association organized an expert panel discussion involving representatives from gastrointestinal surgery, medical oncology, cardiology, dermatology, nephrology, endocrinology, and ophthalmology to consider the systemic clinical symptoms, molecular and cellular mechanisms, and treatment recommendations of GISTs. Here, we present the resultant evidence-and experience-based consensus to guide the management of TKI-associated side events in clinical practice.

Expert consensus of Chinese Association for the Study of Pain on the application of ozone therapy in pain medicine

This consensus was compiled by first-line clinical experts in the field of pain medicine and was organized by the Chinese Association for the Study of Pain.To reach this consensus,we consulted a wide range of opinions and conducted indepth discussions on the mechanism,indications,contraindications,operational specifications and adverse reactions of ozone iatrotechnique in the treatment of pain disorders.We also referred to related previous preclinical and clinical studies published in recent years worldwide.The purpose of this consensus is to standardize the rational application of ozone iatrotechnique in pain treatment,to improve its efficacy and safety and to reduce and prevent adverse reactions and complications in this process.

Expert consensus of the Chinese Association for the Study of Pain on pain treatment with the transdermal patch

Chronic pain lasting more than 3 mo,or even several years can lead to disability.Treating chronic pain safely and effectively is a critical challenge faced by clinicians.Because administration of analgesics through oral,intravenous or intramuscular routes is not satisfactory,research toward percutaneous delivery has gained interest.The transdermal patch is one such percutaneous delivery system that can deliver drugs through the skin and capillaries at a certain rate to achieve a systemic or local therapeutic effect in the affected area.It has many advantages including ease of administration and hepatic first pass metabolism avoidance as well as controlling drug delivery,which reduces the dose frequency and side effects.If not required,then the patch can be removed from the skin immediately.The scopolamine patch was the first transdermal patch to be approved for the treatment of motion sickness by the Food and Drug Administration in 1979.From then on,the transdermal patch has been widely used to treat many diseases.To date,no guidelines or consensus are available on the use of analgesic drugs through transdermal delivery.The pain branch of the Chinese Medical Association,after meeting and discussing with experts and based on clinical evidence,developed a consensus for promoting and regulating standard use of transdermal patches containing analgesic drugs.

Expert panel’s guideline on cervicogenic headache:The Chinese Association for the Study of Pain recommendation

Cervicogenic headache(CEH)has been recognized as a unique category of headache that can be difficult to diagnose and treat.In China,CEH patients are managed by many different specialties,and the treatment plans remain controversial.Therefore,there is a great need for comprehensive evidence-based Chinese experts’recommendations for the management of CEH.The Chinese Association for the Study of Pain asked an expert panel to develop recommendations for a series of questions that are essential for daily clinical management of patients with CEH.A group of multidisciplinary Chinese Association for the Study of Pain experts identified the clinically relevant topics in CEH.A systematic review of the literature was performed,and evidence supporting the benefits and harms for the management of CEH was summarized.Twenty-four recommendations were finally developed through expert consensus voting for evidence quality and recommendation strength.We hope this guideline provides direction for clinicians and patients making treatment decisions for the management of CEH.

Expert consensus of Chinese Association for the Study of Pain on the radiofrequency therapy technology in the Department of Pain

On the basis of continuous improvement in recent years,radiofrequency therapy technology has been widely developed,and has become an effective method for the treatment of various intractable pain.Radiofrequency therapy is a technique that uses special equipment and puncture needles to output ultra-high frequency radio waves and accurately act on local tissues.In order to standardize the application of radiofrequency technology in the treatment of painful diseases,Chinese Association for the Study of Pain(CASP)has developed a consensus proposed by many domestic experts and scholars.

Editorial for the special issue of the Chinese Association for the Study of Pain

The Ministry of Health of China officially issued a document,adding the first level diagnosis and treatment discipline“Algology”in the list of diagnosis and treatment subjects of medical institutions on July 16,2007.As the most important pain academic organization in China,the Chinese Association for the Study of Pain has made outstanding contributions in promoting the development of pain discipline and in establishing pain standards and disease diagnosis and treatment guidelines.In this special issue,under the leadership of Yan-Qing Liu,Chairman of the 7th Committee of the Chinese Association for the Study of Pain,nine consensus and one guideline were included.

Analgesic and anti-inflammatory activity of Cotinus coggygria Scop.extracts in vivo

Objective:To assess the analgesic and anti-inflammatory effects of standardized extract of Cotinus coggygria(C.coggygria)in different animal models.Methods:C.coggygria extracts(25,50,and 100 mg/kg)were administered to rats and mice(n=6)during hot plate,tail-flick,acetic acid-induced writhing,and formalin tests to determine its analgesic efficacy.The anti-inflammatory activity of C.coggygria extracts was evaluated by histamine and carrageenan-induced paw edema,cotton pellet-induced granuloma,and acetic acid-induced peritoneal capillary dye leakage tests.Results:C.coggygria extracts(50 and 100 mg/kg)significantly alleviated thermal and chemical-induced pain in rodents(P<0.05).It also demonstrated notable anti-inflammatory properties by mitigating histamine and carrageenan-induced paw edema,granuloma deposits,and vascular permeability(P<0.05).Moreover,C.coggygria extracts remarkably reduced TNF-α,IL-1β,IL-6,COX-2,and oxidative stress in rat paws(P<0.05).Carrageenan-induced histological aberrations in hind paw tissues were effectively(P<0.05)mitigated by treatment with C.coggygria extracts.Conclusions:C.coggygria Scop.extracts show analgesic and anti-inflammatory effects via inhibition of COX-2 and inflammatory and oxidative mediators.

Enhanced Precision Therapy of Multiple Myeloma Through Engineered Biomimetic Nanoparticles with Dual Targeting

Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@M.The results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in vivo.Additionally,this material demonstrated a capability for drug release triggered by low pH conditions.Moreover,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM cells.Notably,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice.Therefore,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.

Discrete Element Modelling of Damage Evolution of Concrete Considering Meso-Structure of ITZ

The mechanical properties of interfacial transition zones(ITZs)have traditionally been simplified by reducing the stiffness of cement in previous simulation methods.A novel approach based on the discrete element method(DEM)has been developed for modeling concrete.This new approach efficiently simulates the meso-structure of ITZs,accurately capturing their heterogeneous properties.Validation against established uniaxial compression experiments confirms the precision of thismodel.The proposedmodel canmodel the process of damage evolution containing cracks initiation,propagation and penetration.Under increasing loads,cracks within ITZs progressively accumulate,culminating in macroscopic fractures that traverse themortarmatrix,forming the complex,serpentine path of cracks.This study reveals four distinct displacement patterns:tensile compliant,tensile opposite,mixed tensile-shear,and shear opposite patterns,each indicative of different stages in concrete’s damage evolution.The widening angle of these patterns delineates the progression of cracks,with the tensile compliant pattern signaling the initial crack appearance and the shear opposite pattern indicating the concrete model’s ultimate failure.

Hepatocyte growth factor enhances the ability of dental pulp stem cells to ameliorate atherosclerosis in apolipoprotein E-knockout mice

BACKGROUND Atherosclerosis(AS),a chronic inflammatory disease of blood vessels,is a major contributor to cardiovascular disease.Dental pulp stem cells(DPSCs)are capable of exerting immunomodulatory and anti-inflammatory effects by secreting cytokines and exosomes and are widely used to treat autoimmune and inflam-mation-related diseases.Hepatocyte growth factor(HGF)is a pleiotropic cytokine that plays a key role in many inflammatory and autoimmune diseases.AIM To modify DPSCs with HGF(DPSC-HGF)and evaluate the therapeutic effect of DPSC-HGF on AS using an apolipoprotein E-knockout(ApoE-/-)mouse model and an in vitro cellular model.METHODS ApoE-/-mice were fed with a high-fat diet(HFD)for 12 wk and injected with DPSC-HGF or Ad-Null modified DPSCs(DPSC-Null)through tail vein at weeks 4,7,and 11,respectively,and the therapeutic efficacy and mechanisms were analyzed by histopathology,flow cytometry,lipid and glucose measurements,real-time reverse transcription polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay at the different time points of the experiment.An in vitro inflammatory cell model was established by using RAW264.7 cells and human aortic endothelial cells(HAOECs),and indirect co-cultured with supernatant of DPSC-Null(DPSC-Null-CM)or DPSC-HGF-CM,and the effect and mechanisms were analyzed by flow cytometry,RT-PCR and western blot.Nuclear factor-κB(NF-κB)activators and inhibitors were also used to validate the related signaling pathways.RESULTS DPSC-Null and DPSC-HGF treatments decreased the area of atherosclerotic plaques and reduced the expression of inflammatory factors,and the percentage of macrophages in the aorta,and DPSC-HGF treatment had more pronounced effects.DPSCs treatment had no effect on serum lipoprotein levels.The FACS results showed that DPSCs treatment reduced the percentages of monocytes,neutrophils,and M1 macrophages in the peripheral blood and spleen.DPSC-Null-CM and DPSC-HGF-CM reduced adhesion molecule expression in tumor necrosis factor-αstimulated HAOECs and regulated M1 polarization and inflammatory factor expression in lipopolysaccharide-induced RAW264.7 cells by inhibiting the NF-κB signaling pathway.CONCLUSION This study suggested that DPSC-HGF could more effectively ameliorate AS in ApoE-/-mice on a HFD,and could be of greater value in stem cell-based treatments for AS.

Ocular surface in patients with different degrees of myopia

AIM:To investigate the clinical features of the ocular surface in patients with different degrees of myopia.METHODS:A cross-sectional study was conducted involving 122 participants with myopia in Beijing Tongren Hospital from February to June,2023.After completing the Ocular Surface Disease Index(OSDI)score scale,measurements were taken for refraction,biometric parameters and ocular surface parameters.The prevalence,severity and related parameters of the dry eye among different groups based on axial length(AL)were compared.Correlation analysis was performed between ocular surface parameters and refraction/biometric measurement parameters.RESULTS:Statistically significant differences were observed in refractive error,corneal thickness,anterior chamber depth,and subfoveal choroidal thickness among the groups(all P<0.05).With the increase in AL,the incidence and severity of dry eye increased significantly(P<0.05).Moreover,the tear film break-up time(BUT)shortened(P<0.05),and the corneal fluorescein staining(CFS)points increased significantly(P<0.05).OSDI scores were positively correlated with AL and spherical equivalent(SE;both P<0.05);BUT was negatively correlated with AL,SE,and corneal astigmatism(AST;all P<0.05);Schirmer I test(SIT)results were negatively correlated with AL and SE(both P<0.05).CONCLUSION:AL elongation is a risk factor for dry eye onset in myopic participants.The longer the AL,the more severe the dry eye is,with the increased CFS spots and tear film instability.Additionally,SE and AST exhibit negative correlations with dry eye symptom scores and ocular surface parameters.