Cancer is a highly aggressive and devastating disease, and impediments to a cure arise not just from cancer itself. Targeted therapies are difficult to achieve since the majority of cancers are more intricate than ever imagined. Mainstream methodologies including chemotherapy and radiotherapy as routine clinical regimens frequently fail, eventually leading to pathologies that are refractory and incurable. One major cause is the gradual to rapid repopulation of surviving cancer cells during intervals of multiple-dose administration. Novel stress-responsive molecular pathways are increasingly unmasked and show promise as emerging targets for advanced strategies that aim at both de novo and acquired resistance. We highlight recent data reporting that treatments particularly those genotoxic can induce highly conserved damage responses in non-cancerous constituents of the tumor microenvironment (TMEN). Master regulators, including but not limited to NF-kB and C/EBP-β, are implicated and their signal cascades culminate in a robust, chronic and genome-wide secretory program, forming an activated TMEN that releases a myriad of soluble factors. The damage-elicited but essentially off target and cell non-autonomous secretory phenotype of host stroma causes adverse consequences, among which is acquired resistance of cancer cells. Harnessing signals arising from the TMEN, a pathophysiological niche frequently damaged by medical interventions, has the potential to promote overall efficacy and improve clinical outcomes provided that appropriate actions are ingeniously integrated into contemporary therapies. Thereby, anticancer regimens should be well tuned to establish an innovative clinical avenue, and such advancement will allow future oncological treatments to be more specific, accurate, thorough and personalized.
Antineoplastic Agents ; therapeutic use ; CCAAT-Enhancer-Binding Protein-beta ; metabolism ; Humans ; Models, Biological ; Molecular Targeted Therapy ; methods ; trends ; NF-kappa B ; metabolism ; Neoplasms ; drug therapy ; metabolism ; Precision Medicine ; methods ; trends ; Signal Transduction ; drug effects ; Tumor Microenvironment ; drug effects

Objective To explore the determinants of serum uric acid (UA) levels and the relationship between UA and cardiovascular disease in elderly patients.Methods A cross-sectional design was used.A total of 1 066 elderly patients were consecutively recruited in the study.Anthropometric measurement and lifestyle survey were performed,and serum UA,lipid profile,glucose,homocysteine (Hcy) and superoxide dismutase (SOD) were measured.The determinants of serum UA levels and correlation between UA and cardiovascular disease were analyzed by regression.Results The prevalence of hyperuricemia was 21.9％ (25.9％ in men and 18.7％ in women).Partial correlation analysis showed the level of serum UA was positively correlated with Hcy (r=0.163,P=0.000),body mass index (r=0.128,P=0.004) and triglyceride (r=0.133,P=0.003),and negatively correlated with HDL-C (r=-0.103,P=0.021).After adjustment for potential confounding factors,multivariate analysis showed eGFR (β =-2.044,t =-10.544,P =0.000),gender (β =42.065,t=4.700,P=0.000),Hcy (β=1.367,t=3.714,P=0.000),BMI (β=3.370,t=2.706,P=0.007),TG (β=14.120,t=2.589,P=0.010) and SOD (β=-0.636,t=-3.079,P=0.002) were independent determinants for UA levels in elderly patients.Logistic regression analysis indicated that mild elevation of UA levels was a risk factor of hypertension (OR=1.925,95％ CI=1.124-3.295) in women and OR=1.780 (95％ CI=1.010-3.136) in men].High UA levels increased the risk of coronary heart disease in women [OR=1.710 (95％ CI=1.157-2.526)],but decreased the risk of ischemic stroke in men [OR=0.524 (95％ CI=0.335-0.820)].Conclusions In elderly patients,serum UA levels were affected by renal function,gender,BMI and serum Hcy,TG and SOD.Mildly elevated UA levels increased the risk of hypertension.High UA levels increased the risk of coronary heart disease in women and decreased the risk of ischemic stroke in men.

Objective To investigate the effects of risk factors on non thyroidal Illness syndrome (NTIS) in elderly inpatients.Methods A total of 819 elderly inpatients who met inclusion criteria were consecutively recruited in thiscross-sectional study.Physicalmeasurements and mini nutritional assessment using the mini nutritional assessment-short form (MNA-SF) score were conducted.A serum levels of thyroid stimulating hormone (TSH),free triiodothyronine (FT3),free thyroxine (FT4),brain natriuretic peptide (BNP) and C-reactive protein (CRP) were examined.Data were analyzed with multivariatelogistic regression.Results The significant differences were found between NTIS group (n=145) versus control group (n=674)inage (78.5±8.1) years vs.(75.1±8.6) years(t=5.422,P＜0.01),in body mass index (23.0 ±3.8) kg/m2 vs.(24.1±3.6) kg/m2,in MNA-SF score 11.2±2.3 vs.12.3± 1.8(t=-3.315,6.754,P＜0.01),in level of serum albumin (36.0±4.5) g/L vs.(38.4±3.6) g/L (t=-6.977,P＜0.01),in triglyceride level (1.3± 0.9) mmol/L vs.(1.5±1.0) mmol/L(t=-3.039,P＜0.01),inCRP (Z=-8.857,P＜0.01)),and in BNP (t=6.331,P＜0.01).Logistic regression analysis revealed that age＞ =80 years (OR=2.433,95％CI:1.357 4.361),malnutrition (OR=1.946,95％CI:1.261-3.001),renal insufficiency (eG FR＜60 ml/min,OR =2.131,95％ CI:1.367-3.322),and high level of CRP (10 mg/L and 50 mg/L:OR=3.446,95％CI:2.117-5.611;over 50 mg/L:OR =10.029,95％CI:4.693-21.432,all P＜0.01)) were risk factors for NTIS.Conclusions Non-thyroidal illness syndrome in elderly inpatients is correlated with advanced age,renal insufficiency,malnutrition and stress,which are the independent risk factors.

Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell acti-vators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside Ⅳ,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory compo-nents of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.

Objective:To investigate the clinical effect of local perforator advancement flap in repairing mid-face soft tissue defects and its correlation between with the three dimensional configuration of the skin ligament.Methods:1) 12 fresh adult cadaver specimens (7 males, 5 females, aged 54-87 years) were selected. After dehydration and degreasing of the cadaver head with acetone, plasticized and sliced with a fully transparent ultra-thin layer of epoxy resin, using a Leica MZ8 stereo microscope and a Leica DFC295 digital camera to observe and analyze the prepared slices, and observe the differences in the three-dimensional structural characteristics of the cutaneous ligaments in different parts of the midface (cheek, nose, orbital eyelid) . (2) A retrospective analysis was made of the case data of midface soft tissue defects admitted to the Plastic Surgery Department of the First Affiliated Hospital of Anhui Medical University from January 2015 to October 2021. All patients were repaired with local perforator advancement flap. The Pearson bivariate correlation test was used to analyze the correlation among flap advancement distance, flap area, flap aspect ratio, and defect size. The Kruskal-Wallis test was used to analyze the differences of flap area and flap aspect ratio in different parts of the midface.Results:1) Anatomical studies have shown that the running direction of the facial skin ligaments is the same as that of the expressive muscles, and their three-dimensional structures at the upper eyelid and the nasal and facial corners of the upper nasal alar are different. The upper eyelid skin ligaments run along the eyelid, while the upper nasal The supracutaneous ligaments run down the alar of the nose. (2) The clinical study included 18 patients, 8 males and 10 females, aged (65.1±22.9) years. The flaps of 18 patients survived after operation, the flap area was (13.85±9.38) cm 2, and the advancing distance was (1.94±0.75) cm. Statistical analysis showed that there was a correlation between the flap advancement distance and the flap incision area ( r=-0.712, P=0.022) and the flap aspect ratio ( r=-0.580, P =0.012). There was no correlation with the defect area ( r=-0.227, P=0.365) ; the aspect ratios of the cheek, nose and orbital lid flaps were 2.06±0.42 , 2.50±1.18, 3.25±0.93, and the differences were statistically significant ( H= 6.59, P=0.037). Conclusions:The local perforator advancement flap is an ideal method for repairing midface soft tissue defects. The differences in the construction of the skin ligaments in different parts of the mid-face will affect the ease of advancement of the flaps and other characteristics in each part, which may be the reasons for affecting the aspect ratio of the flap design.

Objective:To investigate the clinical effect of local perforator advancement flap in repairing mid-face soft tissue defects and its correlation with the three-dimensional configuration of the skin ligament.Methods:(1) Tweleve fresh adult cadaver specimens, including seven males and five females, aged 54-87 years old, were selected. After dehydration and degreasing of the cadaver head with acetone, plasticized and sliced with a fully transparent ultra-thin layer of epoxy resin, using a Leica MZ8 stereo microscope and a Leica DFC295 digital camera to observe and analyze the prepared slices and observe the differences in the three-dimensional structural characteristics of the cutaneous ligaments in different parts of the mid-face (cheek, nose, orbital eyelid). (2) A retrospective study was conducted with the data of mid-face soft tissue defects admitted to the Department of Plastic Surgery of the First Affiliated Hospital of Anhui Medical University from January 2015 to October 2021. All patients were repaired with local perforator advancement flaps. The Pearson bivariate correlation test was used to analyze the correlation among flap advancement distance, flap area, flap aspect ratio, and defect size. The Kruskal-Wallis test was used to analyze the differences in flap size and aspect ratio in different parts of the mid-face. The measurement data were described by Mean±SD or M( Q1, Q3). Results:(1) Anatomical studies have shown that the running direction of the facial skin ligaments is the same as that of the expressive muscles, and their three-dimensional structures at the upper eyelid and the nasal and facial corners of the upper nasal alar are different. The upper eyelid skin ligaments run along the eyelid, while the upper nasal cutaneous ligaments run down the nose alar. (2) The clinical study included 18 patients, including eight males and ten females, aged (64.6±23.4) years old. All flaps survived uneventfully. The average flap size was 10.6(8.0, 18.0) cm 2, and the average advancing distance was 2.8(2.0, 4.0) cm. Statistical analysis showed a correlation between the flap advancement distance, the flap incision area ( r=-0.71, P=0.022), and the flap aspect ratio ( r=-0.58, P=0.012). There was no correlation with the defect area ( r=-0.23, P=0.365); the aspect ratios of the cheek, nose, and orbital lid flaps were 2.1(1.9, 2.3), 2.0(1.6, 3.5), 3.5(3.0, 4.0), and the differences were statistically significant ( H=6.59, P=0.037). Conclusions:The local perforator advancement flap is an ideal method for repairing mid-face soft tissue defects. The differences in the construction of the skin ligaments in different parts of the mid-face will affect the ease of advancement of the flaps and other characteristics in each part, which may be the reasons for affecting the aspect ratio of the flap design.

Objective:To investigate the clinical effect of local perforator advancement flap in repairing mid-face soft tissue defects and its correlation between with the three dimensional configuration of the skin ligament.Methods:1) 12 fresh adult cadaver specimens (7 males, 5 females, aged 54-87 years) were selected. After dehydration and degreasing of the cadaver head with acetone, plasticized and sliced with a fully transparent ultra-thin layer of epoxy resin, using a Leica MZ8 stereo microscope and a Leica DFC295 digital camera to observe and analyze the prepared slices, and observe the differences in the three-dimensional structural characteristics of the cutaneous ligaments in different parts of the midface (cheek, nose, orbital eyelid) . (2) A retrospective analysis was made of the case data of midface soft tissue defects admitted to the Plastic Surgery Department of the First Affiliated Hospital of Anhui Medical University from January 2015 to October 2021. All patients were repaired with local perforator advancement flap. The Pearson bivariate correlation test was used to analyze the correlation among flap advancement distance, flap area, flap aspect ratio, and defect size. The Kruskal-Wallis test was used to analyze the differences of flap area and flap aspect ratio in different parts of the midface.Results:1) Anatomical studies have shown that the running direction of the facial skin ligaments is the same as that of the expressive muscles, and their three-dimensional structures at the upper eyelid and the nasal and facial corners of the upper nasal alar are different. The upper eyelid skin ligaments run along the eyelid, while the upper nasal The supracutaneous ligaments run down the alar of the nose. (2) The clinical study included 18 patients, 8 males and 10 females, aged (65.1±22.9) years. The flaps of 18 patients survived after operation, the flap area was (13.85±9.38) cm 2, and the advancing distance was (1.94±0.75) cm. Statistical analysis showed that there was a correlation between the flap advancement distance and the flap incision area ( r=-0.712, P=0.022) and the flap aspect ratio ( r=-0.580, P =0.012). There was no correlation with the defect area ( r=-0.227, P=0.365) ; the aspect ratios of the cheek, nose and orbital lid flaps were 2.06±0.42 , 2.50±1.18, 3.25±0.93, and the differences were statistically significant ( H= 6.59, P=0.037). Conclusions:The local perforator advancement flap is an ideal method for repairing midface soft tissue defects. The differences in the construction of the skin ligaments in different parts of the mid-face will affect the ease of advancement of the flaps and other characteristics in each part, which may be the reasons for affecting the aspect ratio of the flap design.

Objective:To investigate the clinical effect of local perforator advancement flap in repairing mid-face soft tissue defects and its correlation with the three-dimensional configuration of the skin ligament.Methods:(1) Tweleve fresh adult cadaver specimens, including seven males and five females, aged 54-87 years old, were selected. After dehydration and degreasing of the cadaver head with acetone, plasticized and sliced with a fully transparent ultra-thin layer of epoxy resin, using a Leica MZ8 stereo microscope and a Leica DFC295 digital camera to observe and analyze the prepared slices and observe the differences in the three-dimensional structural characteristics of the cutaneous ligaments in different parts of the mid-face (cheek, nose, orbital eyelid). (2) A retrospective study was conducted with the data of mid-face soft tissue defects admitted to the Department of Plastic Surgery of the First Affiliated Hospital of Anhui Medical University from January 2015 to October 2021. All patients were repaired with local perforator advancement flaps. The Pearson bivariate correlation test was used to analyze the correlation among flap advancement distance, flap area, flap aspect ratio, and defect size. The Kruskal-Wallis test was used to analyze the differences in flap size and aspect ratio in different parts of the mid-face. The measurement data were described by Mean±SD or M( Q1, Q3). Results:(1) Anatomical studies have shown that the running direction of the facial skin ligaments is the same as that of the expressive muscles, and their three-dimensional structures at the upper eyelid and the nasal and facial corners of the upper nasal alar are different. The upper eyelid skin ligaments run along the eyelid, while the upper nasal cutaneous ligaments run down the nose alar. (2) The clinical study included 18 patients, including eight males and ten females, aged (64.6±23.4) years old. All flaps survived uneventfully. The average flap size was 10.6(8.0, 18.0) cm 2, and the average advancing distance was 2.8(2.0, 4.0) cm. Statistical analysis showed a correlation between the flap advancement distance, the flap incision area ( r=-0.71, P=0.022), and the flap aspect ratio ( r=-0.58, P=0.012). There was no correlation with the defect area ( r=-0.23, P=0.365); the aspect ratios of the cheek, nose, and orbital lid flaps were 2.1(1.9, 2.3), 2.0(1.6, 3.5), 3.5(3.0, 4.0), and the differences were statistically significant ( H=6.59, P=0.037). Conclusions:The local perforator advancement flap is an ideal method for repairing mid-face soft tissue defects. The differences in the construction of the skin ligaments in different parts of the mid-face will affect the ease of advancement of the flaps and other characteristics in each part, which may be the reasons for affecting the aspect ratio of the flap design.

Objective To investigate the correlation between salivary cystatin D level and salivary gland injury in patients with primary Sj?gren syndrome(pSS).Methods A total of 51 pSS patients admitted in the Department of Rheumatology and Immunology of the First Affiliated Hospital of Xi'an Jiaotong University from September 1,2022 to June 30,2023,and 51 age-and gender-matched healthy individuals who took physical examination in the hospital during same period were enrolled in the study.The level of salivary cystatin D was detected,and the difference in the level between the 2 groups was compared using an independent-samples t test.Pearson correlation analysis was applied to analyze the correlation between salivary cystatin D and clinical parameters in the patients.Results The pSS patients had significantly lower cystatin D level than the healthy controls(206.55±108.11 vs 374.32±172.24 pg/mL,P＜0.01).The cystatin D level in the pSS patients was positively correlated with both static(r=0.433,P=0.002)and dynamic salivary flow rates(r=0.363,P=0.009).The patients with higher score of salivary gland ultrasonography(SGUS)had obviously lower cystatin D than those with lower SGUS score(parotid gland:160.75±85.56 vs 290.53±95.17 pg/mL,P＜0.01;submandibular gland:157.76±87.59 vs 276.25±97.06 pg/mL,P＜0.01).The cystatin D level was also negatively correlated with peripheral blood IL-6 level(r=-0.453,P=0.001)and CD4+T cell count(r=-0.396,P=0.005)in the pSS patients.Conclusion Salivary cystatin D level can be used as an indicator of salivary gland damage for pSS patients.

Objective To investigate the predictive value of preoperative blood inflammatory markers for the recurrence risk in patients with basal cell carcinoma(BCC).Methods A total of 225 patients with BCC were divided into the high-risk recurrence group(155 cases)and the low-risk recurrence group(70 cases).General information and preoperative hematological indicators were collected in the two groups of patients.The neutrophil-to-lymphocyte ratio(NLR),lymphocyte-to-monocyte ratio(LMR),systemic inflammation marker(SIM)and platelet-to-lymphocyte ratio(PLR)were calculated.Receiver operating characteristic(ROC)curves were used to determine the predictive value of hematological markers with statistically significant differences between the two groups for BCC recurrence and to establish optimal cutoff values.Univariate and multivariate Logistic regression analyses were conducted to identify factors influencing BCC recurrence.A multivariate Logistic regression model was established to predict the recurrence risk of BCC.Area under the curve(AUC)and the Hosmer-Lemeshow test were used to evaluate the prediction efficiency and goodness-of-fit of the model.Results ROC analysis identified that optimal cutoff values for LMR and SIM were 5.12 and 0.86,respectively.Univariate Logistic regression analysis showed that LMR,SIM,ulceration at the primary tumor site,UV exposure and tumor maximum diameter were factors influencing BCC recurrence.Multivariate Logistic regression revealed that SIM≥0.86,tumor maximum diameter≥2.0 cm and UV exposure were risk factors for BCC recurrence,while LMR≥5.12 had a protective effect.The Logistic prediction model for BCC recurrence risk was Logit(P)=-1.598-1.517×LMR+1.323×SIM+2.406×UV exposure+3.465×tumor maximum diameter,with good model fit(P=0.725)and an AUC of 0.869(95%CI:0.822-0.917)for predicting BCC recurrence risk.Conclusion Monitoring preoperative LMR and SIM levels can assist in assessing the risk of recurrence in BCC patients and provide important guidance for clinical decision-making.