BACKGROUND: Concurrent chemo-radiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer (LACC), but there are still many patients who suffer tumor recurrence. However, valuable predictors of treatment outcomes remain limited. This study aimed to assess the value of the serum immune biomarkers to predict the prognosis. METHODS: We reviewed cervical cancer patients treated with CCRT between January 2014 and May 2018 at Peking Union Medical College Hospital. The systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and lactate dehydrogenase (LDH) were calculated using blood samples. The relationship between immune markers and the treatment outcome was analyzed. The area under the receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency. The Cox proportional hazards model and log-rank were used to predict overall survival (OS) and disease-free survival (DFS). RESULTS: This study included 667 patients. Among them, 195 (29.2%) patients were defined as treatment failure, including 127 (19.0%) patients with pelvic failure, 94 (14.1%) distant failure, and 25 (3.7%) concurrent pelvic and distant failure. It revealed that the tumor stage, size, metastatic lymph nodes (MLNs), and serum immune biomarkers, such as SII, SIRI, and LDH, were significantly related to treatment outcomes. We demonstrated that the optimal cut-off of the SII, SIRI, and LDH were 970.4 × 10 9 /L, 1.3 × 10 9 /L, and 207.52 U/L, respectively. Importantly, this study presented that LDH level had the highest OR (OR = 4.2; 95% CI [2.3-10.8]). Furthermore, the OS and DFS for patients with pre-SII ≥970.5 × 10 9 /L were significantly worse than those with pre-SII <970.5 × 10 9 /L. Similarly, pre-SIRI ≥1.25 × 10 9 /L and pre-LDH ≥207.5 U/L were related to poor survival outcomes. CONCLUSIONS This study demonstrated that the baseline SII, SIRI, and LDH levels can be used to accurately and effectively predict the treatment outcomes after CCRT and long-term prognosis. Our results may offer additional prognostic information in clinical, which helps to detect the potential recurrent metastasis in time.
Humans ; Female ; Uterine Cervical Neoplasms/drug therapy* ; Middle Aged ; Adult ; Aged ; Chemoradiotherapy/methods* ; L-Lactate Dehydrogenase/blood* ; Treatment Outcome ; Disease-Free Survival ; Prognosis ; ROC Curve ; Biomarkers, Tumor/blood* ; Proportional Hazards Models

The statement"Blood is the material carrier of spirit and qi"indicates that the generation of blood relies on the coordinated governance of spirit and qi,while simultaneously serving as their material foundation.Based on the physiological connection among"blood-spirit-qi",this article explores the pathogenesis of premature ovarian insufficiency(POI)accompanied by anxiety and depression.It proposes that essence and blood deficiency,premature exhaustion of Tian Gui(reproductive essence),and failure of blood to nourish the spirit form a pathological chain:"blood deficiency-spirit disturbance-POI with anxiety and depression".Blood stasis obstructing the uterine chamber,disorder of the chong and ren meridians,and failure of blood to carry the spirit give rise to the transformation:"blood stasis-spirit depression-POI with anxiety and depression".Liver qi stagnation and disruption of qi and blood further exacerbate the imbalance between blood and spirit,aggravating the disease progression.Based on this pathological analysis,the general treatment principle of"regulating blood,harmonizing spirit,and rectifying qi"is established.For patients with blood deficiency syndrome,treatment should focus on tonifying essence and blood,replenishing reproductive essence,and nourishing the spirit,selecting Guanyuan(CV4),Zusanli(ST36),and Sanyinjiao(SP6)as main acupoints.For patients with blood stasis syndrome,treatment should aim to regulate the chong and ren meridians,promote blood circulation,and calm the spirit,selecting Qichong(ST30),Zhongji(CV3),and Xuehai(SP10)as main acupoints.Simultaneously,the method of regulating the liver should be applied throughout the entire treatment process to soothe the liver,regulate qi,relieve depression,and calm the spirit,selecting Baihui(GV20),Taichong(LR3),and Ganshu(BL18)as main acupoints.Appropriate acupuncture techniques and methods should be chosen according to the patient's constitution and condition,providing new therapeutic ideas and approaches for clinical practice.

Objective To analyze the molecular epidemiology of Candida tropicalis(C.tropicalis)isolates from bloodstream infections,and to investigate preliminarily the underlying mechanisms of fluconazole resistance.Methods Clinical C.tropicalis isolates were collected from bloodstream infections at West China Hospital,Sichuan University and other hospitals in Sichuan Province.All the collected isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry,and the antifungal susceptibility test was performed by the broth microdilution method.Multilocus sequence typing(MLST)was conducted using the first generation sequencing technique.Genes associated with drug-resistance were sequenced and the mutation sites were identified.The relative expression levels of genes associated with drug-resistance were analyzed using reverse transcription-quantitative polymerase chain reaction(RT-qPCR).Results A total of 39 C.tropicalis isolates from bloodstream infections were collected.The MLST phylogenetic tree showed that most of the strains clustered in the phylogenetic tree shared identical or similar minimal inhibitory concentrations(MICs).All MLST types were not matched with the isolates in the PubMLST database,representing new diploid sequence types(DSTs).A total of 3 sense mutations,including Ser154Phe,Tyr132Phe,and Tyr257His were identified in ERG11,and were present only in drug-resistant strains.UPC2 contained 4 sense mutations,including Ala251Thr,Gln289Leu,Ser279Glu,and Gln313His,which were also present only in drug-resistant strains.Ser279Glu and Gln313His were previously unreported.There were two sense mutations in ERG3,namely Ser112Gly and Ala48Ser,both being previously unreported,and Ser112Gly was found only in drug-resistant strains.The expression levels of ERG11(14.48 vs 7.109,P=0.003)and UPC2(1.922 vs 0.832,P=0.04)in non-sensitive group(MIC>2 mg/L)were higher than those in sensitive group(MIC≤2 mg/L),and the difference was statistically significant.Conclusion There may be a unique genetic relationship among C.tropicalis isolates from Sichuan province,and the MICs of fluconazole against C.tropicalis are associated with molecular typing.ERG11 mutations were the major mechanism underlying fluconazole resistance in C.tropicalis isolates.The upregulation of ERG11 and UPC2 was associated with fluconazole resistance in C.tropicalis.

Sound financing mechanism is an important support for the development of health system.In response to the problems exposed in the health system during the COVID-19 pandemic,OECD countries have proposed intervention directions and investment strategies to strengthen the resilience of the health system.The investment allocation in strengthening core public health capabilities,proactive material reserves,and coordinated supply from OECD countries were analyzed,in order to explore the characteristics and effectiveness,which could provide a reference for strengthening the resilience of China's health system.

Sound financing mechanism is an important support for the development of health system.In response to the problems exposed in the health system during the COVID-19 pandemic,OECD countries have proposed intervention directions and investment strategies to strengthen the resilience of the health system.The investment allocation in strengthening core public health capabilities,proactive material reserves,and coordinated supply from OECD countries were analyzed,in order to explore the characteristics and effectiveness,which could provide a reference for strengthening the resilience of China's health system.

Sound financing mechanism is an important support for the development of health system.In response to the problems exposed in the health system during the COVID-19 pandemic,OECD countries have proposed intervention directions and investment strategies to strengthen the resilience of the health system.The investment allocation in strengthening core public health capabilities,proactive material reserves,and coordinated supply from OECD countries were analyzed,in order to explore the characteristics and effectiveness,which could provide a reference for strengthening the resilience of China's health system.

Sound financing mechanism is an important support for the development of health system.In response to the problems exposed in the health system during the COVID-19 pandemic,OECD countries have proposed intervention directions and investment strategies to strengthen the resilience of the health system.The investment allocation in strengthening core public health capabilities,proactive material reserves,and coordinated supply from OECD countries were analyzed,in order to explore the characteristics and effectiveness,which could provide a reference for strengthening the resilience of China's health system.

Sound financing mechanism is an important support for the development of health system.In response to the problems exposed in the health system during the COVID-19 pandemic,OECD countries have proposed intervention directions and investment strategies to strengthen the resilience of the health system.The investment allocation in strengthening core public health capabilities,proactive material reserves,and coordinated supply from OECD countries were analyzed,in order to explore the characteristics and effectiveness,which could provide a reference for strengthening the resilience of China's health system.

Sound financing mechanism is an important support for the development of health system.In response to the problems exposed in the health system during the COVID-19 pandemic,OECD countries have proposed intervention directions and investment strategies to strengthen the resilience of the health system.The investment allocation in strengthening core public health capabilities,proactive material reserves,and coordinated supply from OECD countries were analyzed,in order to explore the characteristics and effectiveness,which could provide a reference for strengthening the resilience of China's health system.

Sound financing mechanism is an important support for the development of health system.In response to the problems exposed in the health system during the COVID-19 pandemic,OECD countries have proposed intervention directions and investment strategies to strengthen the resilience of the health system.The investment allocation in strengthening core public health capabilities,proactive material reserves,and coordinated supply from OECD countries were analyzed,in order to explore the characteristics and effectiveness,which could provide a reference for strengthening the resilience of China's health system.