Ischemia-reperfusion (I/R) injury following skin flap transplantation is a critical factor leading to flap necrosis and transplant failure. Antagonizing inflammatory responses and oxidative stress are regarded as crucial targets for mitigating reperfusion injury and enhancing flap survival. In this study, caffeic acid-vanadium metal polyphenol nanoparticles (CA-V NPs) were prepared for the treatment of skin flap ischemia and reperfusion. This study was conducted using a one-step method to prepare new types of CA-V NPs with uniform sizes and stable structures. In vitro, the CA-V NPs exhibited CAT-like and SOD-like activities and could effectively scavenge ROS, generate oxygen, and alleviate oxidative stress. In the H₂O₂-induced cellular oxidative stress model, CA-V NPs effectively reduced ROS levels and inhibited apoptosis through the XIAP/Caspase-3 pathway. In the cellular inflammation model induced by LPS combined with IFN-γ, CA-V NPs reprogrammed macrophage polarization toward the M2 phenotype and reduced inflammatory responses by reducing the expression of the chemokines CCL4 and CXCL2. In addition, animal experiments have shown that CA-V NPs can alleviate oxidative stress in skin flap tissues, inhibit apoptosis, promote angiogenesis, and ultimately improve the survival rate of skin flaps. CA-V NPs provide a new target and strategy for the treatment of flap I/R injury.

Objective:To explore the longitudinal predictive relationship between self-neglect and frailty among older adults.Methods:Data were drawn from the Chinese Longitudinal Healthy Longevity Survey conducted in 2011 (T1), 2014 (T2), and 2018 (T3). A total of 1 495 older adults aged≥65 years at T1 who participated in three consecutive surveys and had no missing key variables were included. General demographic information, self-neglect scores, and frailty status were extracted. Spearman correlation analysis was used to examine the association between self-neglect and frailty. Cross-lagged analysis was employed to investigate the potential causal relationship between the two variables.Results:The self-neglect scores for 1 495 older adults at T1, T2, and T3 were (2.84±1.39), (2.47±1.30), and (2.41±1.20), respectively, showing a declining trend. The frailty scores at T1, T2, and T3 were 0 (0, 1.00), 0 (0, 2.00), and 1.00 (0, 2.00), respectively, indicating an increasing trend. Cross-lagged analysis revealed that self-neglect at T1 positively predicted frailty at T2 (β=0.076, P=0.004). Frailty at both T1 and T2 positively predicted self-neglect at T2 (β=0.057, P=0.044) and T3 (β=0.058, P=0.029), respectively. Conclusions:Frailty among older adults positively predicts self-neglect, and self-neglect also has a certain predictive effect on frailty. Medical staff should strengthen early screening and intervention for frailty in older adults to delay the occurrence and progression of self-neglect.

Objective:To explore the longitudinal predictive relationship between self-neglect and frailty among older adults.Methods:Data were drawn from the Chinese Longitudinal Healthy Longevity Survey conducted in 2011 (T1), 2014 (T2), and 2018 (T3). A total of 1 495 older adults aged≥65 years at T1 who participated in three consecutive surveys and had no missing key variables were included. General demographic information, self-neglect scores, and frailty status were extracted. Spearman correlation analysis was used to examine the association between self-neglect and frailty. Cross-lagged analysis was employed to investigate the potential causal relationship between the two variables.Results:The self-neglect scores for 1 495 older adults at T1, T2, and T3 were (2.84±1.39), (2.47±1.30), and (2.41±1.20), respectively, showing a declining trend. The frailty scores at T1, T2, and T3 were 0 (0, 1.00), 0 (0, 2.00), and 1.00 (0, 2.00), respectively, indicating an increasing trend. Cross-lagged analysis revealed that self-neglect at T1 positively predicted frailty at T2 (β=0.076, P=0.004). Frailty at both T1 and T2 positively predicted self-neglect at T2 (β=0.057, P=0.044) and T3 (β=0.058, P=0.029), respectively. Conclusions:Frailty among older adults positively predicts self-neglect, and self-neglect also has a certain predictive effect on frailty. Medical staff should strengthen early screening and intervention for frailty in older adults to delay the occurrence and progression of self-neglect.

Immune checkpoint inhibitor-related pneumonitis(CIP)is a relatively common immune-related adverse event.The current treatment for CIP mainly relies on glucocorticoids,with 70％～80％of patients being controlled by conventional glucocorticoid therapy.However,steroid-unresponsive CIP is often se-vere and can be life-threatening.There is no standard treatment protocol for steroid-unresponsive CIP,highlighting a significant unmet clinical need.This paper reviews the diagnosis,treatment progress,and exploratory research of steroid-unresponsive CIP to provide evidence-based guidelines and directions for clinical and translational research.

Immune checkpoint inhibitor-related pneumonitis(CIP)is a relatively common immune-related adverse event.The current treatment for CIP mainly relies on glucocorticoids,with 70％～80％of patients being controlled by conventional glucocorticoid therapy.However,steroid-unresponsive CIP is often se-vere and can be life-threatening.There is no standard treatment protocol for steroid-unresponsive CIP,highlighting a significant unmet clinical need.This paper reviews the diagnosis,treatment progress,and exploratory research of steroid-unresponsive CIP to provide evidence-based guidelines and directions for clinical and translational research.

Objective:To investigate the characteristics of infectious pathogens in patients with refractory prostatitis,and to detect serum levels of factors related to immune inflammatory response such as macrophage inflammatory protein 1α(MIP-1α),IL-8 and cyclooxygenase-2(COX-2).Methods:A total of 87 patients with refractory chronic prostatitis who were diagnosed and treated in the Outpatient Department of Zhengzhou Ninth People's Hospital and Andrology Outpatient Department of Zhengzhou Central Hospital from October 2018 to June 2020 were selected as observation group,and 87 healthy subjects were selected as control group.Analyzed characteristics of infectious pathogens in patients with refractory prostatitis,compared serum MIP-1α,IL-8,COX-2 levels and the dif-ferent efficacy of the two groups,clinical data of the two groups of patients,serum MIP-1α,IL-8,COX-2 levels before and after treat-ment,and to analyze the correlation of the difference of serum MIP-1α,IL-8,COX-2 and the duration of the disease,the National Institutes of Health-Chronic Prostatitis Symptom Index(NIH-CPSI),maximum urinary flow rate and the relationship between serum MIP-1α,IL-8,COX-2 diffe-rence and the efficacy of patients with refractory prostatitis,and to evaluate the assessment value of serum MIP-1α,IL-8,COX-2 difference on the efficacy of patients with refractory prostatitis.Results:Bacterial infection was present in 87 specimens of prostatic fluid from patients with refractory prostatitis,and 9 patients had concomitant mycoplasma infection.From the prostatic fluid samples of 87 patients with refractory prostatitis,a total of 338 pathogenic bacteria were isolated,including 230 gram-positive bacteria,accounting for 68.05%;108 gram-negative bacteria,accounting for 31.95%;serum MIP-1α,IL-8,COX-2 levels in observation group were higher than that in control group,the difference was statistically significant(P<0.05);the course of disease,NIH-CPSI score,maximum urinary flow rate,levels of MIP-1α,IL-8,COX-2 after treatment,and the difference of MIP-1α,IL-8,COX-2 before and after treatment were compared in patients with different curative effects,and the difference was statistically signifi-cant(P<0.05);the difference between serum MIP-1α,IL-8 and COX-2 in patients with refractory prostatitis before and after treat-ment was positively correlated with disease course and NIH-CPSI score,while negatively correlated with maximum urinary flow rate(P<0.05);the differences of serum MIP-1α,IL-8 and COX-2 before and after treatment were significantly correlated with curative effect of patients with refractory prostatitis(P<0.05);AUC values of serum MIP-1α,IL-8 and COX-2 before and after treatment to evaluate the efficacy of refractory prostatitis patients were 0.856,0.819 and 0.788,respectively,and the combined AUC value was the largest,which was 0.903.Conclusion:Pathogenic bacteria in patients with refractory prostatitis are mainly gram-positive bacteria,and the serum MIP-1α,IL-8 and COX-2 are significantly increased,which are closely related to the evolution of the disease.They can be used to evaluate clinical efficacy,and provide information for subsequent treatment.

ObjectiveTo screen the differential markers by analyzing volatile components in Dalbergia odorifera and its counterfeits， in order to provide reference for authentication of D. odorifera. MethodThe volatile components in D. odorifera and its counterfeits were detected by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the GC conditions were heated by procedure（the initial temperature of the column was 50 ℃， the retention time was 1 min， and then the temperature was raised to 300 ℃ at 10 ℃ for 10 min）， the carrier gas was helium， and the flow rate was 1.0 mL·min^-1， the split ratio was 10∶1， and the injection volume was 1 mL. The MS conditions used electron bombardment ionization（EI） with the scanning range of m/z 35-550. The compound species were identified by database matching， the relative content of each component was calculated by the peak area normalization method， and principal component analysis（PCA）， orthogonal partial least squares-discrimination analysis（OPLS-DA） and cluster analysis were performed on the detection results by SIMCA 14.1 software， and the differential components of D. odorifera and its counterfeits were screened out according to the variable importance in the projection（VIP） value>2 and P<0.05. ResultA total of 26， 17， 8， 22， 24 and 7 volatile components were identified from D. odorifera， D. bariensis， D. latifolia， D. benthamii， D. pinnata and D. cochinchinensis， respectively. Among them， there were 11 unique volatile components of D. odorifera， 6 unique volatile components of D. bariensis， 3 unique volatile components of D. latifolia， 6 unique volatile components of D. benthamii， 8 unique volatile components of D. pinnata， 4 unique volatile components of D. cochinchinensis. The PCA results showed that， except for D. latifolia and D. cochinchinensis， which could not be clearly distinguished， D. odorifera and other counterfeits could be distributed in a certain area， respectively. The OPLS-DA results showed that D. odorifera and its five counterfeits were clustered into one group each， indicating significant differences in volatile components between D. odorifera and its counterfeits. Finally， a total of 31 differential markers of volatile components between D. odoriferae and its counterfeits were screened. ConclusionHS-GC-MS combined with SIMCA 14.1 software can systematically elucidate the volatile differential components between D. odorifera and its counterfeits， which is suitable for rapid identification of them.

Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.

Objective:To investigate the levels of glypican 3 (GPC3) and alpha-fetoprotein (AFP) in the serum of patients with primary liver cancer and its diagnostic value in liver cancer.Methods:A total of 277 patients with primary liver cancer, 108 patients with gastric cancer, 40 patients with hepatitis alone, 19 patients with hepatitis combined with other cancers other than liver cancer and 54 healthy controls in Shanxi Provincial Cancer Hospital between June 2018 and January 2019 were collected. The serum samples from all patients were taken. Enzyme linked immunosorbent assay (ELISA) was used to detect GPC3 level in all specimens. Electrochemiluminescence was used to detect the level of AFP. The diagnostic value of GPC3 or AFP alone and a combination of both for liver cancer was also compared. The relationship between GPC3 and AFP was also analyzed.Results:The serum GPC3 level [median (interquartile range)] in primary liver cancer, gastric cancer, the hepatitis only, the hepatitis combined with other cancer and healthy control was 0.079 ng/ml (0.198 ng/ml), 0.048 ng/ml (0.044 ng/ml), 0.073 ng/ml (0.053 ng/ml), 0.050 ng/ml (0.018 ng/ml), 0.023 ng/ml (0.011 ng/ml), respectively. The GPC3 level in the primary liver cancer was higher than that in the gastric cancer, hepatitis combined with other cancers other than liver cancer, the healthy controls (all P < 0.05), and there was no statistically significant difference in the level of GPC3 between the primary liver cancer and the hepatitis only ( P = 0.520). The sensitivity and specificity of GPC3 for the diagnosis of primary liver cancer was 69.5% and 94.4%, respectively. The sensitivity and specificity of AFP for the diagnosis of primary liver cancer was 63.9% and 94.0%, respectively. The sensitivity and specificity of the combined detection of liver cancer was 80.2% and 94.3%, respectively. The ratio of positive likelihood ratio and negative likelihood ratio was 38.42, 27.73 and 67.01, respectively in liver cancer diagnosed with GPC3, AFP and both of them. The expression of serum GPC3 was associated with AFP ( r = 0.34, P < 0.01). Conclusions:The detection of GPC3 combined with AFP can increase the detection rate of primary liver cancer, and it has a certain clinical significance in the early screening and diagnosis of primary liver cancer.

Objective: To assess the current evidence regarding the efficacy, safety, and potential advantages of endoscopic compared with open salvage surgery for patients with local recurrent nasopharyngeal carcinoma. Methods: A systematic search of Pubmed/Medline, Embase, and Cochrane databases ranged between 2000 and 2017 was conducted. Included studies reported specific residual or local recurrent nasopharyngeal cancer survival data. Proportional Meta-analysis was performed on both outcomes with a random-effects model and the 95% confidential intervals were calculated by Stata 12.0 software. Results: A total of 24 case series studies were included in the Meta-analysis.The pooled 2-year overall survival rates of endoscopic and open group were 84% (95%CI:72%-93%), 68%(95%CI:59%-77%),respectively.The pooled 2-year disease-free survival rates of endoscopic and open group were 68%(95%CI:53%-81%), 65%(95%CI:54%-75%),respectively. The pooled 5-year overall survival rates of endoscopic and open group were 72%(95%CI:37%-97%), 48% (95%CI:40%-56%),respectively.The pooled 5-year disease-free survival rates of endoscopic and open group were 65%(95%CI:29%-93%), 50%(95%CI:43%-57%),respectively.The combined outcome of endoscopic was higher than open procedure. In addition, less severe complications, lower local recurrence rates(27%vs32%).The 2-year overall survival rates of endoscopic was higher than open procedure in the staging of rT1, rT2, and rT3 (93%vs87%; 77%vs63%; 67%vs53%) , but was equal to open in the staging for rT4 (35%vs35%) .Meta-regression showed that the heterogeneity was correlated with advanced tumor ratio. Conclusions The present Meta-analysis reveals that endoscopic approach offers a safe and efficient alternative to open approach with better short-term outcome and fewer postoperative complications in selecting patients strictly.