[摘 要] 目的：探讨复发/转移性鼻咽癌（NPC）接受含PD-1单抗免疫治疗的临床特征和预后影响因素。方法：回顾性分析2019年3月至2024年7月期间南部战区总医院确诊的95例NPC患者的临床资料和外周血生化及免疫学指标。预后分析采用Kaplan-Meier曲线，组间比较使用Log-rank检验，采用Cox比例风险模型进行单因素和多因素分析。结果：95例患者中男性81例，女性14例，中位年龄49.72岁（16~74岁），Ⅳ期91例（95.79%），所有患者均采用免疫治疗，联合或不联合化疗方案治疗，中位无进展生存期（mPFS）为10.5个月，客观缓解率（ORR）70.53%，疾病控制率（DCR）89.47%，接受含铂治疗方案患者PFS相对更长，且差异有统计学意义。紫杉醇 + 顺铂 + 氟尿嘧啶（TPF）对比吉西他滨 + 顺铂（GP）和紫杉醇 + 顺铂（TP）显示出更长的PFS，但差异无统计学意义。不同PD-1单抗治疗组间的PFS未显示出有统计学意义的差异。单因素及多因素Cox回归分析结果显示，肿瘤复发状态、初始血浆EBV感染状态、治疗周期数、基线外周血SII是复发/转移性NPC患者接受PD-1抑制剂治疗疗效预测的独立相关因素（均P < 0.05），并且非复发患者、初始血浆EBV DNA阳性、接受 ≥ 4治疗周期、基线外周血SII < 772.81的患者接受PD-1抑制剂治疗预后相对更好。结论：在接受PD-1抑制剂治疗的复发/转移性NPC患者中，非复发患者、初始血浆EBV DNA阳性、≥ 4治疗周期且外周血SII < 772.81者PFS相对更长，可早期识别免疫治疗效果不佳患者并精准干预。

Stroke is the leading cause of death and disability among adults in China， and its common complications include digestive system abnormalities， cognitive impairment， depression， stroke-associated pneumonia， and hemiplegia. The combination of traditional Chinese and Western medicine has great potential in treating post-stroke complications. Xinglou Chengqitang （XLCQT） is a representative prescription of alleviating the disease in the upper part by treating the lower part. It has definite therapeutic effect and high safety. Clinically， XLCQT is often used to treat stroke and its complications. However， the quantity and quality of clinical trials of XLCQT in treating post-stroke complications need to be improved. Additionally， since the basic research is weak， the material basis and multi-target mechanism for the efficacy of this prescription are unknown. This article reviews XLCQT in terms of the pharmacodynamic basis， medicinal properties， safety evaluation， and progress in clinical research and mechanisms in treating post-stroke complications. This article summarizes 22 key active ingredients of XLCQT in treating acute stroke complicated with syndrome of phlegm heat and fu-organ excess. Among these key active ingredients， resveratrol， kaempferol， luteolin， chrysoeriol， apigenin， （+）-catechin， and adenosine have good pharmacokinetic properties and high bioavailability. The mechanisms of XLCQT in treating post-stroke complications are complex， including inflammatory response， brain-gut axis， hypothalamic-pituitary-adrenal （HPA） axis， intestinal flora， neurotrophic factors， autophagy， oxidative stress， and free radical damage. This review helps to deeply understand the pharmacodynamic basis and mechanisms of XLCQT in treating post-stroke complications and provides a theoretical basis for the clinical application of XLCQT against post-stroke complications and the development of drugs.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Objective To explore the effect of myotubularin-related protein 6(MTMR6)on the invasion of hepatocellular carcinoma cell line HepG2 and the potential molecular mechanism.Methods By analyzing the sequencing results of liver cancer tissues and adjacent tissues in Gene Expression Omnibus(GEO)database,MTMR6 gene was screened out,and Spearman analysis was used to analyze the correlation of MTMR6 and pathway in the Cancer Genome Atlas(TCGA)database.Finally,the interaction between MTMR6 and signaling pathway proteins was analyzed with Genemania database.Then the expression of MTMR6 in human normal liver cell line LO-2 and hepatoma cell lines Huh-7 and HepG2 were measured and compared among the cell lines.Then HepG2 cells was selected as the study object.After MTMR6 gene was knocked down or over-expressed in HepG2 cells,Transwell assay was employed to observe invasion ability,and Western blotting was adopted to detect the expression of MTMR6,PI3K,p-PI3K,AKT,p-AKT,mTOR,p-mTOR MMP-2 and MMP-9.Results The expression of MTMR6 was significantly higher in the hepatocellular carcinoma tissues than the paracancer tissues,and it was in a positive linear correlation with PI3K/AKT/mTOR signaling pathway(P＜0.01),showing interaction with PI3K,AKT and mTOR.The expression level of MTMR6 was significantly higher in the HepG2 cells than the LO-2 and Huh-7 cells(P＜0.01).Over-expression of MTMR6 obviously enhanced invasion ability(P＜0.01),while its knockdown decreased the ability(P＜0.01)in HepG2 cells.Knockdown of MTMR6 gene also resulted in decreased phosphorylation of PI3K,AKT and mTOR,and expression levels of MMP-2 and MMP-9(P＜0.01),while over-expression of MTMR6 promoted the phosphorylation of PI3K,AKT and mTOR,and up-regulated the expression of MMP-2 and MMP-9(P＜0.01).In addition,LY294002(a specific PI3K inhibitor)treatment could block the PI3K/AKT/mTOR pathway and down-regulate the expression of MMP-2 and MMP-9(P＜0.01),but had no effect on MTMR6 expression.Conclusion MTMR6 may promote the invasion of hepatoma cells through activation of PI3K/AKT/mTOR signaling pathway.

BACKGROUND: Ischemic acute kidney injury (AKI) is a common syndrome associated with considerable mortality and healthcare costs. Up to now, the underlying pathogenesis of ischemic AKI remains incompletely understood, and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking. Here, this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing (scRNA-seq) analysis in kidneys. METHODS: In this study, scRNA-seq technology was applied to kidneys from two ischemic AKI patients, and three human public scRNA-seq datasets were collected as controls. Differentially expressed genes (DEGs) and cell clusters of kidneys were determined. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as the ligand-receptor interaction between cells, were performed. We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion (I/R) injury induced AKI mice through immunohistochemistry staining. RESULTS: 15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control. The injured proximal tubules (PT) displayed a proapoptotic and proinflammatory phenotype. PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47 , RASSF4 , EBAG9 , IER3 , SASH1 , SEPTIN7 , and NUB1 , which have not been reported in ischemic AKI previously. Several hub genes were validated in kidneys from human AKI and renal I/R injury mice, respectively. Furthermore, PT highly expressed DEGs enriched in endoplasmic reticulum stress, autophagy, and retinoic acid-inducible gene I (RIG-I) signaling. DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain (NOD)-like receptor signaling, estrogen signaling, interleukin (IL)-12 signaling, and IL-17 signaling. Overexpressed genes in kidney-resident immune cells including macrophages, natural killer T (NKT) cells, monocytes, and dendritic cells were associated with leukocyte activation, chemotaxis, cell adhesion, and complement activation. In addition, the ligand-receptor interactions analysis revealed prominent communications between macrophages and monocytes with other cells in the process of ischemic AKI. CONCLUSION Together, this study reveals distinct cell-specific transcriptomic atlas of kidney in ischemic AKI patients, altered signaling pathways, and potential cell-cell crosstalk in the development of AKI. These data reveal new insights into the pathogenesis and potential therapeutic strategies in ischemic AKI.
Humans ; Mice ; Animals ; Transcriptome/genetics* ; Ligands ; Kidney/metabolism* ; Acute Kidney Injury/metabolism* ; Ischemia/metabolism* ; Reperfusion Injury/metabolism* ; Sequence Analysis, RNA ; Adaptor Proteins, Signal Transducing/metabolism* ; Tumor Suppressor Proteins/metabolism*

Objective:To investigate the protective mechanism of TAK242, a specific inhibitor of Toll-like receptor 4 (TLR4), on the liver of septic rats.Methods:Eighteen male Sprague-Dawley (SD) rats were randomly divided into three groups ( n = 6 in each group). The septic model was established by intraperitoneal injection of lipopolysaccharide (LPS) 15 mg/kg. The rats in the TAK242 intervention group received intraperitoneal injection of TAK242 (5 mg/kg) before modeling, while the rats in the septic model group and the control group were injected with the same amount of solvent [10% dimethyl sulfoxide (DMSO) + 90% corn oil]. Six hours later, the blood of abdominal aorta was collected and the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by enzyme linked immunosorbent assay (ELISA). The rats were sacrificed to obtain liver, the expression levels of TLR4, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cysteinyl aspartate-specific proteinase-3 (caspase-3), nuclear factor-κB p65 (NF-κB p65) and phosphorylated NF-κB p65 (p-NF-κB p65) were detected by Western blotting. Immunohistochemical staining was used to observe NF-κB p65 protein expression in liver, and hepatocyte injury was assessed by hematoxylin-eosin (HE) staining. Results:Serum ALT and AST levels in the septic model group were significantly higher than those in the control group [ALT (μg/L): 26.639±7.814 vs. 2.847±2.150, AST (μg/L): 28.442±8.417 vs. 5.779±3.019, both P < 0.01]. The ALT and AST levels in the TAK242 intervention group were significantly lower than those in septic model group [ALT (μg/L): 7.269±3.398 vs. 26.639±7.814, AST (μg/L): 3.580±3.115 vs. 28.442±8.417, both P < 0.01]. Light microscopy showed that the hepatocytes in the septic model group were disordered, with obvious cell edema and increased inflammatory cells infiltration; the hepatocytes in the TAK242 intervention group were more neatly arranged, with significantly reduced hepatocyte edema and reduced inflammatory cells infiltration. Western blotting results showed that caspase-3 protein expression in hepatic tissue of septic model group was significantly higher than that in the control group (caspase-3/GAPDH: 0.794±0.164 vs. 0.482±0.055, P < 0.05), and caspase-3 protein expression in the TAK242 intervention group significantly decreased than that in the septic model group (caspase-3/GAPDH: 0.482±0.056 vs. 0.794±0.164, P < 0.05), which indicated that TAK242 could attenuate hepatocytes apoptosis of septic rats. The expression of IL-6, TNF-α and TLR4 protein and the ratio of p-NF-κB p65/NF-κB p65 in hepatic tissue of septic model group were significantly higher than those in control group (IL-6/GAPDH: 1.442±0.204 vs. 1.019±0.024, TNF-α/GAPDH: 1.089±0.098 vs. 0.806±0.005, TLR4/GAPDH: 1.292±0.085 vs. 0.941±0.087, p-NF-κB p65/NF-κB p65 ratio: 1.936±0.081 vs. 1.579±0.183, all P < 0.05), IL-6, TNF-α and TLR4 protein expression and p-NF-κB p65/NF-κB p65 ratio in the TAK242 intervention group were significantly lower than those in septic model group (IL-6/GAPDH: 1.035±0.042 vs. 1.442±0.204, TNF-α/GAPDH: 0.572±0.096 vs. 1.089±0.098, TLR4/GAPDH: 0.984±0.078 vs. 1.292±0.085, p-NF-κB p65/NF-κB p65 ratio: 1.484±0.255 vs. 1.936±0.081, all P < 0.05), it is suggested that LPS-induced sepsis could activate the inflammatory response mediated by TLR4/NF-κB pathway in liver, and the activation of TLR4/NF-κB pathway was inhibited by TAK242 through the TLR4 pathway, therefore, the inflammation of liver in septic rats was reduced. Immunohistochemical staining showed that the positive expression of NF-κB p65 in liver was significantly increased in the septic model group compared with the control group; the positive expression of NF-κB p65 was significantly reduced in the TAK242 intervention group compared with the septic model group, and there was almost no positive expression in the nucleus. Conclusion:TAK242 could reduce liver function injury and protect the liver by inhibition TLR4/NF-κB pathway in septic rats.

Objective:To understand the research hotspots of external fixation nursing in the past 5 years and analyze the research status and development trend of this field, so as to provide a reference for external fixation nursing practice and research development in China.Methods:PubMed, Web of Science, China National Knowledge Internet (CNKI), Wanfang Database and VIP database were used to retrieve external fixation nursing related literature published from August 2015 to July 2020. Bibliographic information data mining system software and graph clustering toolkit software were used to perform bibliometric and cluster analysis.Results:A total of 720 literatures were included, including 318 English literatures and 402 Chinese literatures. A total of 25 English high-frequency words were extracted with frequency greater than or equal to 23 times, and 17 Chinese high-frequency words were extracted with frequency greater than or equal to 25 times. After cluster analysis, two English research hotspots were obtained, namely, information acquisition and application in nursing research, functional recovery after external fixation. Five Chinese research hotspots were obtained, including the prevention of needle-path infection, the nursing effect of systematic nursing on patients with external fixation, application of negative pressure sealing drainage technology in open fractures, perioperative nursing of patients with bone defects and rehabilitation nursing of fractures at different locations.Conclusions:It is possible to use information management and big data to analyze the risk factors of external fixation care for prevention, and to standardize the external fixation care process through standardized procedures and the introduction of nursing guidelines for different parts of the external fixation. At the same time, attention should be paid to the functional recovery of patients with external fixation in order to improve the nursing quality of external fixation.

Objective:To investigate the effect of rapamycin on hepatic ischemia-reperfusion injury (HIRI) in Sprague Dawley (SD) rats and its underlying mechanism.Methods:Forty-eight specific pathogen-free SD male rats with the body weight of 180-200 g and the age of 4-8 weeks were randomly divided into 3 groups, 16 rats each group. In the rapamycin group, the rats were injected with rapamycin intraperitoneally everyday lasting for 3 days before the surgery, and in the model group and the sham group, the rats were injected with normal saline intraperitoneally. The HIRI model was performed in the rapamycin group and the model group. Serum of 8 rats was randomly harvested from each group at 2 h and 24 h after the surgery and was used to detect level of alanine aminotransferase(ALT), total bilirubin, and lactate dehydrogenase. At the meantime, liver tissues were collected for HE staining, and enzyme-linked immunosorbent assay of superoxide dismutase(SOD), glutathione, hexokinase 2, phosphofructokinase 1(PFK1), and adenosine triphosphate. Polymerase chain reaction and Western blots were used to determine the levels of mammalian target of rapamycin(mTOR), ribosomal protein S6 kinase 1(S6K1), and protein kinase B and their phosphorylation levels respectively.Results:Two hours post the surgery, the serum level of ALT(150.9±18.7) U/L, total bilirubin(5.15±0.69) μmol/L, and lactate dehydrogenase(9 547±365) U/L were higher in the model group than sham group (42.4±10.7) U/L, (2.48±0.24) μmol/L, (4 424±376) U/L and rapamycin group (87.7±11.2) U/L, (3.09±0.12) μmol/L, (8 268±264) U/L, and all differences were statistically significant (all P<0.05). HE staining and serum assay showed that the lesion of liver tissuesand of liver function were damaged in the model group, and mitigated in the rapamycin group at 2h and 24h after the surgery. At 2h and 24h after the surgery, liver SOD, glutathione, hexokinase 2, PFK1, and adenosine triphosphate in the model group were lower than those in the sham group and the rapamycin group, and all differences were statistically significant (all P<0.05). The relative levels of mTOR, S6K1, and their phosphorylation level in the model group were higher than those in the sham group and the rapamycin group at 2 h and 24 h after the surgery, but the relative levels of protein kinase B and phosphorylated protein kinase B were lower than those in the sham group and the rapamycin group, and all differences were statistically significant (all P<0.05). Conclusions:Rapamycin improves glucose metabolism and reduces oxidative stress via upregulating the phosphorylated protein kinase B through inhibition of mTOR signaling pathway, thus alleviates HIRI in rats.

Objective:To compare the therapeutic effects of nasal high-flow oxygen therapy (HFNC) and nasal canal oxygenation (NCO) during breaks off non-invasive ventilation (NIV) for acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and to explore the feasibility of NIV combined with HFNC in the treatment of AECOPD.Methods:From August 2017 to July 2019, AECOPD patients with type Ⅱrespiratory failure (arterial blood gas pH <7.35, PaCO 2 > 50 mmHg) who were treated with NIV were randomly (random number) assigned to the HFNC group and NCO group at 1:1. The HFNC group received HFNC treatment during breaks from NIV and the NCO group received low-flow NCO during the NIV interval. The primary endpoint was the total respiratory support time. The secondary endpoints were endotracheal intubation, duration of NIV treatment and breaks from NIV, length of ICU stay, total length of hospital stay and so on. Results:Eighty-two patients were randomly assigned to the HFNC group and the NCO group. After secondary exclusion, 36 patients in the HFNC group and 37 patients in the NCO group were included in the analysis. The total respiratory support time in the HFNC group was significantly shorter than that in the NCO group [(74 ± 18) h vs. (93 ± 20) h, P = 0.042]. The total duration of NIV treatment in the HFNC group was significantly shorter than that in the NCO group [(36 ± 11) h vs. (51 ± 13) h, P=0.014]. There was no significant difference of the mean duration of single break from NIV between the two groups, but durations of break from NIV in the HFNC group were significantly longer than those in the NCO group since the third break from NIV ( P < 0.05). The intubation rates of the HFNC and NCO groups were 13.9% and 18.9%, respectively, with no significant difference ( P=0.562). The length of ICU stay in the HFNC group was (4.3 ± 1.7) days, which was shorter than that in the NCO group [(5.8 ± 2.1) days, P=0.045], but there was no significant difference in the total length of hospital stay between the two groups. Heart rate, respiratory rate, percutaneous carbon dioxide partial pressure and dyspnea score during the breaks from NIV in the NCO group were significantly higher than those in the HFNC group, and the comfort score was lower than that in the HFNC group ( P<0.05). Conclusion:For AECOPD patients receiving NIV, compared with NCO, HFNC during breaks from NIV can shorten respiratory support time and length of ICU stay, and improve carbon dioxide retention and dyspnea. HFNC is an ideal complement to NIV therapy in AECOPD patients.

Objective To investigate the predictive value of metabolic syndrome in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI).Methods A total of 660 patients with ACS admited to cardiovascular department,first affiliated hospital of zhengzhou university were enrolled in this study from January 2009 to June 2010.The enrollment criteria were:the stenosis degree were above 75％ in at least one coronary artery by coronary angiography and successful PCI procedure.Exculsion criteria were:liver and renal insufficiency,malignancies and valvular heart diseases.The relevant clinical data and labtory examination were recorded after admission. The patients were followed up by outpatients interview or telephone from March to June 2011 and adverse cardiovascular events were recorded.The patients were divided into MS and non-MS groups,and basic clinical data were compared between two groups.The proportion difference between two groups were tested by chi square. Multivariate logistic regression was established to analyze the factors related to progonosis.The survival ratio was estimated using the Kaplan-Meier method.Statistical significance was established at a P value of less than 0.05.Results ①A total of 606 (91.7％) patients successfully accepted follow-up.Mean follow-up time were ( 14.3 ±1.7 ) months.95 patients experienced adverse cardiovascular events ( 15.7％ ).②There were 393 patients (64.96％ ) satisfied the definition of metabolic syndrome.The patients in MS group were with higher BMI,SBP,DBP,blood glucose and disordered lipid (all P ＜ 0.05 ),with less fale patients (P =0.016),less current somking (P =0.008 ) and with higher platelet (P =0.037 ). The incidence of adverse cardiovascular events in two groups were 17.81％ and 11.79％ ( P ＞ 0.05 ). ③ Multivarite logistic regression revealed that the predictors of adverse cardiovascular events were age [ OR =2.628,95％ confidence interval (CI) 1.395 ～ 4.954,P =0.003 ],New York Heart Association (NYHA) ≥ 3 grade ( OR =2.310,95％ CI 1.095 ～4.870,P =0.028) and left ventricular ejection fraction (LVEF) ( OR =4.328,95％ CI 1.955 ～9.580,P ＜ 0.001 ).However,MS was not related with prognosis ( OR =1.170,95％ CI 0.583 ～ 2.345,P =0.659 ).④The cumulative survival rates of no adverse cardiovascular events in the two groups were no significant difference ( P ＞ 0.05 ).Conclusions MS is a risk factor with coronary heart disease.Howerer,it has no relationship with adverse cardiovascular events in patients with ACS after PCI.